Mechanisms of RecQ helicases in pathways of DNA metabolism and maintenance of genomic stability

Biochemical Journal

Volumn 398, Issue 3, 2006, Pages 319-337

  Sharma, Sudha ^a   Doherty, Kevin M ^a   Brosh Jr , Robert M ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Aging; Cancer; DNA repair; Genomic instability; Helicase; RecQ

Indexed keywords

AGING OF MATERIALS; CATALYSTS; DISEASES; DNA; GENES; HYDROLYSIS; METABOLISM; TUMORS;

DNA REPAIR; GENOMIC INSTABILITY; MOLECULAR MOTOR PROTEINS; RECQ HELICASES;

PROTEINS;

ANTHRAQUINONE DERIVATIVE; DNA POLYMERASE; DOUBLE STRANDED DNA; ESCHERICHIA COLI PROTEIN; EXONUCLEASE; MISMATCH REPAIR PROTEIN PMS2; N METHYLMESOPORPHYRIN IX; PERYLENE; PORPHYRIN DERIVATIVE; RECOMBINANT PROTEIN; RECQ HELICASE; REPLICATION PROTEIN A; RIBONUCLEASE III; SINGLE STRANDED DNA; SMALL INTERFERING RNA; TELOMERASE INHIBITOR; UNCLASSIFIED DRUG; WERNER SYNDROME PROTEIN; ADENOSINE TRIPHOSPHATASE; DNA; HELICASE; RECQL PROTEIN, HUMAN;

AGING; CANCER; CANCER CELL; CANCER CHEMOTHERAPY; CARBOXY TERMINAL SEQUENCE; CARCINOGENESIS; CATALYSIS; CHROMOSOMAL INSTABILITY; CHROMOSOME DAMAGE; CONFORMATIONAL TRANSITION; DNA ADDUCT; DNA BINDING; DNA DAMAGE; DNA METABOLISM; DNA RECOMBINATION; DNA REPAIR; DNA REPLICATION; DNA STRAND BREAKAGE; DNA STRUCTURE; ENZYME ACTIVITY; ENZYME POLYMORPHISM; ENZYME SPECIFICITY; ENZYME STRUCTURE; EUKARYOTE; EXCISION REPAIR; GENOMIC INSTABILITY; HUMAN; MUTATIONAL ANALYSIS; NONHUMAN; ONCOGENE C MYC; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN LOCALIZATION; PROTEIN MOTIF; PROTO ONCOGENE; REVIEW; RNA TRANSCRIPTION; SEQUENCE HOMOLOGY; SISTER CHROMATID EXCHANGE; TELOMERE; YEAST; METABOLISM;

ADENOSINE TRIPHOSPHATASES; DNA; DNA HELICASES; GENOMIC INSTABILITY; HUMANS; RECQ HELICASES;

EID: 33748744378     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/BJ20060450     Document Type: Review

References (285)

1. Harrigan, J. A. and Bohr, V. A. (2003) Human diseases deficient in RecQ helicases. Biochimie 85, 1185-1193
2. Agrelo, R., Cheng, W. H., Setien, F., Ropero, S., Espada, J., Fraga, M. F., Herranz, M., Paz, M. F., Sanchez-Cespedes, M., Artiga, M. J. et al. (2006) Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc. Natl. Acad. Sci. U.S.A. 103, 8822-8827
3. Siitonen, H. A., Kopra, O., Kaariainen, H., Haravuori, H., Winter, R. M., Säämänen, A. M., Peltonen, L. and Kestila, M. (2003) Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Hum. Mol. Genet. 12, 2837-2844
4. Van Maldergem, L., Siitonen, H. A., Jalkh, N., Chouery, N., De Roy, M., Delague, V., Muenke, M., Jabs, E. W., Cai, J., Wang, L. L. et al. (2006) Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene. J. Med. Genet. 43, 148-152
5. Kyng, K. J., May, A., Kolvraa, S. and Bohr, V. A. (2003) Gene expression profiling in Werner syndrome closely resembles that of normal aging. Proc. Natl. Acad. Sci. U.S.A. 100, 12259-12264
6. Kyng, K. J., May, A., Stevnsner, T., Becker, K. G., Kolvra, S. and Bohr, V. A. (2005) Gene expression responses to DNA damage are altered in human aging and in Werner Syndrome. Oncogene 24, 5026-5042
7. Bennett, R. J. and Keck, J. L. (2004) Structure and function of RecQ DNA helicases. Crit. Rev. Biochem. Mol. Biol, 39, 79-97
8. Bernstein, D. A. and Keck, J. L. (2003) Domain mapping of Escherichia coli RecQ defines the roles of conserved N- and C-terminal regions in the RecQ family. Nucleic Acids Res. 31, 2778-2785
9. Onoda, F., Seki, M., Miyajima, A. and Enomoto, T. (2000) Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene. Mutat. Res. 459, 203-209
10. Ellis, N. A. and German, J. (1996) Molecular genetics of Bloom's syndrome. Hum. Mol. Genet. 5, 1457-1463
11. Bahr, A., De Graeve, F., Kedinger, C. and Chatton, B. (1998) Point mutations causing Bloom's syndrome abolish ATPase and DNA helicase activities of the BLM protein. Oncogene 17, 2565-2571
12. Bernstein, D. A., Zittel, M. C. and Keck, J. L. (2003) High-resolution structure of the E. coli RecQ helicase catalytic core. EMBO J. 22, 4910-4921
13. Brosh, Jr, R. M., Orren, D. K., Nehlin, J. O., Ravn, P. H., Kenny, M. K., Machwe, A. and Bohr, V. A. (1999) Functional and physical interaction between WRN helicase and human replication protein A. J. Biol. Chem. 274, 18341-18350
14. Neff, N. F., Ellis, N. A., Ye, T. Z., Noonan, J., Huang, K., Sanz, M. and Proytcheva, M. (1999) The DNA helicase activity of BLM is necessary for the correction of the genomic instability of Bloom syndrome cells. Mol. Biol. Cell 10, 665-676
15. Sharma, S., Sommers, J. A., Choudhary, S., Faulkner, J. A., Cui, S., Andreoli, L., Vindigni, A. and Brosh, Jr, R. M. (2005) Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1. J. Biol. Chem. 280, 28072-28084
16. Garcia, P. L., Liu, Y., Jiricny, J., West, S. C. and Janscak, P. (2004) Human RECQ5β, a protein with DNA helicase and strand-annealing activities in a single polypeptide. EMBO J. 23, 2882-2891
17. Lu, J., Mullen, J. R., Brill, S. J., Kleff, S., Romeo, A. M. and Sternglanz, R. (1996) Human homologues of yeast helicase. Nature (London) 383, 678-679
18. Zittel, M. C. and Keck, J. L. (2005) Coupling DNA-binding and ATP hydrolysis in Escherichia coli RecQ: role of a highly conserved aromatic-rich sequence. Nucleic Acids Res. 33, 6982-6991
19. Korotev, S., Hsieh, J., Gauss, G. H., Lohman, T. M. and Waksman, G. (1997) Major domain swiveling revealed by the crystal structures of complexes of E. coli Rep helicase bound to single-stranded DNA and ADP. Cell 90, 635-647
20. Velankar, S. S., Soultanas, P., Dillingham, M. S., Subramanya, H. S. and Wigley, D. B. (1999) Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism. Cell 97, 75-84
21. Liu, J. L., Rigolet, P., Dou, S. X., Wang, P. Y. and Xi, X. G. (2004) The zinc finger motif of Escherichia coli RecQ is implicated in both DNA binding and protein folding. J. Biol. Chem. 279, 42794-42802
22. Guo, R. B., Rigolet, P., Zargarian, L., Fermandjian, S. and Xi, X. G. (2005) Structural and functional characterizations reveal the importance of a zinc binding domain in Bloom's syndrome helicase. Nucleic Acids Res. 33, 3109-3124
23. Hu, J. S., Feng, H., Zeng, W., Lin, G.-X. and Xi, X. G. (2005) Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein. Proc. Natl. Acad. Sci. U.S.A. 102, 18379-18384
24. Lee, J. W., Kusumoto, R., Doherty, K. M., Lin, G.-X., Zeng, W., Cheng, W.-H., von Kobbe, C., Brosh, Jr, R. M. and Bohr, V. A. (2005) Modulation of Werner syndrome protein function by a single mutation in the conserved RecQ domain. J. Biol. Chem. 280, 39627-39636
25. von Kobbe, C., Thoma, N. H., Czyzewski, B. K., Pavletich, N. P. and Bohr, V. A. (2003) Werner syndrome protein contains three structure specific DNA binding domains. J. Biol. Chem. 278, 52997-53006
26. Lee, J. W., Harrigan, J., Opresko, P. L. and Bohr, V. A. (2005) Pathways and functions of the Werner syndrome protein. Mech. Ageing Dev. 126, 79-86
27. Liu, Z., Macias, M. J., Bottomley, M. J., Stier, G., Linge, J. P., Nilges, M., Bork, P. and Sattler, M. (1999) The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins. Structure 7, 1557-1566
28. Bernstein, D. A. and Keck, J. L. (2005) Conferring substrate specificity to DNA helicases: role of the RecQ HRDC domain. Structure 13, 1173-1182
29. Killoran, M. P. and Keck, J. L. (2006) Three HRDC domains differentially modulate Deinococcus radiodurans RecQ DNA helicase biochemical activity. J. Biol. Chem. 281, 12849-12857
30. Moser, M. J., Holley, W. R., Chatterjee, A. and Mian, I. S. (1997) The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains. Nucleic Acids Res. 25, 5110-5118
31. Balajee, A. S., Machwe, A., May, A., Gray, M. D., Oshima, J., Martin, G. M., Nehlin, J. O., Brosh, Jr, R. M., Orren, D. K. and Bohr, V. A. (1999) The Werner syndrome protein is involved in RNA polymerase II transcription. Mol. Biol. Cell 10, 2655-2668
32. Doherty, K. M., Sommers, J. A., Gray, M. D., Lee, J. W., von Kobbe, C., Thoma, N. H., Kureekattil, R. P., Kenny, M. K. and Brosh, Jr, R. M. (2005) Physical and functional mapping of the RPA interaction domain of the Werner and Bloom syndrome helicases. J. Biol. Chem. 280, 29494-29505
33. Ellis, N. A., Groden, J., Ye, T. Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M. and German, J. (1995) The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83, 655-666
34. Janscak, P., Garcia, P. L., Hamburger, F., Makuta, Y., Shiraishi, K., Imai, Y., Ikeda, H. and Bickle, T. A. (2003) Characterization and mutational analysis of the RecQ core of the Bloom syndrome protein. J. Mol. Biol. 330, 29-42
35. Perry, J. J., Yannone, S. M., Holden, L. G., Hitomi, C., Asaithamby, A., Han, S., Cooper, P. K., Chen, D. J. and Tainer, D. J. (2006) WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing. Nat. Struct. Mol. Biol. 13, 414-422
36. Beese, L. S. and Steitz, T. A. (1991) Structural basis for the 3′-5′ exonuclease activity of Escherichia coli DNA polymerase I: a two metal ion mechanism. EMBO J. 10, 25-33
37. Patel, S. S. and Donmez, I. (2006) Mechanisms of helicases. J. Biol. Chem. 281, 18265-18268
38. Eoff, R. L. and Raney, K. D. (2005) Helicase-catalysed translocation and strand separation. Biochem. Soc. Trans. 33, 1474-1478
39. Byrd, A. K. and Raney, K. D. (2004) Protein displacement by an assembly of helicase molecules aligned along single-stranded DNA. Nat. Struct. Mol. Biol. 11, 531-538
40. Byrd, A. K. and Raney, K. D. (2005) Increasing the length of the single-stranded overhang enhances unwinding of duplex DNA by bacteriophage T4 Dda helicase. Biochemistry 44, 12990-12997
41. Bennett, R. J., Sharp, J. A. and Wang, J. C. (1998) Purification and characterization of the Sgs1 DNA helicase activity of Saccharomyces cerevisiae. J. Biol. Chem. 273, 9644-9650
42. Brosh, Jr, R. M., Karow, J. K., White, E. J., Shaw, N. D., Hickson, I. D. and Bohr, V. A. (2000) Potent inhibition of Werner and Bloom helicases by DNA minor groove binding drugs. Nucleic Acids Res. 28, 2420-2430
43. Cui, S., Arosio, D., Doherty, K. M., Brosh, Jr, R. M., Falaschi, A. and Vindigni, A. (2004) Analysis of the unwinding activity of the dimeric RECQ1 helicase in the presence of human replication protein A. Nucleic Acids Res. 32, 2158-2170
44. Macris, M. A., Krejci, L., Bussen, W., Shimamoto, A. and Sung, P. (2006) Biochemical characterization of the RECQ4 protein, mutated in Rothmund-Thomson syndrome. DNA Repair 5, 172-180
45. Orren, D. K., Brosh, Jr, R. M., Nehlin, J. O., Machwe, A., Gray, M. D. and Bohr, V. A. (1999) Enzymatic and DNA binding properties of purified WRN protein: high affinity binding to single-stranded DNA but not to DNA damage induced by 4NQO. Nucleic Acids Res. 27, 3557-3566
46. Harmon, F. G. and Kowalczykowski, S. C. (2001) Biochemical characterization of the DNA helicase activity of the Escherichia coli RecQ helicase. J. Biol. Chem. 276, 232-243
47. Choudhary, S., Sommers, J. A. and Brosh, Jr, R. M. (2004) Biochemical and kinetic characterization of the DNA helicase and exonuclease activities of Werner syndrome protein. J. Biol. Chem. 279, 34603-34613
48. Opresto, P. L., Cheng, W. H. and Bohr, V. A. (2004) At the junction of RecQ helicase biochemistry and human disease. J. Biol. Chem. 279, 18099-18102
49. Xu, H. Q., Deprez, E., Zhang, A. H., Tauc, P., Ladjimim, M. M., Brochon, J. C., Auclaire, C. and Xi, X. G. (2003) The Escherichia coli RecQ helicase functions as a monomer. J. Biol. Chem. 278, 34925-34933
50. Zhang, X. D., Dou, S. X., Xie, P., Hu, J. S., Wang, P. Y. and Xi, X. G. (2006) E. coli RecQ is a rapid, efficient and monomeric helicase. J. Biol. Chem. 281, 12655-12663
51. Brosh, Jr, R. M., Waheed, J. and Sommers, J. A. (2002) Biochemical characterization of the DNA substrate specificity of Werner syndrome helicase. J. Biol. Chem. 277, 23236-23245
52. Ozsoy, A. Z., Ragonese, H. M. and Matson, S. W. (2003) Analysis of helicase activity and substrate specificity of Drosophila RECQ5. Nucleic Acids Res. 31, 1554-1564
53. Ralf, C., Hickson, I. D. and Wu, L. (2006) The Bloom's syndrome helicase can promote the regression of a model replication fork. J. Biol. Chem., doi:10.1074/jbc.M604268200
54. Constantinou, A., Tarsounas, M., Karow, J. K., Brosh, Jr, R. M., Bohr, V. A., Hickson, I. D. and West, S. C. (2000) Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep. 1, 80-84
55. Karow, J. K., Constantinou, A., Li, J. L., West, S. C. and Hickson, I. D. (2000) The Bloom's syndrome gene product promotes branch migration of Holliday junctions. Proc. Natl. Acad. Sci. U.S.A. 97, 6504-6508
56. Bennett, R. J., Keck, J. L. and Wang, J. C. (1999) Binding specificity determines polarity of DNA unwinding by the Sgs1 protein of S. cerevisiae. J. Mol. Biol. 289, 235-248
57. Harmon, F. G. and Kowalczykowski, S. C. (1998) RecQ helicase, in concert with RecA and SSB proteins, initiates and disrupts DNA recombination. Genes Dev. 12, 1134-1144
58. Sharma, S., Otterlei, M., Sommers, J. A., Driscoll, H. C., Dianov, G. L., Kao, H. I., Bambara, R. A. and Brosh, Jr, R. M. (2004) WRN helicase and FEN-1 form a complex upon replication arrest and together process branch-migrating DNA structures associated with the replication fork. Mol. Biol. Cell 15, 734-750
59. van Brabant, A. J., Ye, T., Sanz, M., German, III, J. L., Ellis, N. A. and Holloman, W. K. (2000) Binding and melting of D-loops by the Bloom syndrome helicase. Biochemistry 39, 14617-14625
60. Opresko, P. L., Otterlei, M., Graakjaer, J., Bruheim, P., Dawut, I., Kolvraa, S., May, A., Seidman, M. M. and Bohr, V. A. (2004) The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Mol. Cell 14, 763-774
61. Orren, D. K., Theodore, S. and Machwe, A. (2002) The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry 41, 13483-13488
62. Bachrati, C. Z., Borts, R. H. and Hickson, I. D. (2006) Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase. Nucleic Acids Res. 34, 2269-2279
63. Han, H. and Hurley, L. H. (2000) G-quadruplex DNA: a potential target for anti-cancer drug design. Trends Pharmacol. Sci. 21, 136-142
64. n. J. Biol. Chem. 274, 12797-12802
65. Mohaghegh, P., Karow, J. K., Brosh, Jr, R. M., Bohr, V. A. and Hickson, I. D. (2001) The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases. Nucleic Acids Res. 29, 2843-2849
66. Sun, H., Karow, J. K., Hickson, I. D. and Maizels, N. (1998) The Bloom's syndrome helicase unwinds G4 DNA. J. Biol. Chem. 273, 27587-27592
67. Sun, H., Bennett, R. J. and Maizels, N. (1999) The Saccharomyces cerevisiae Sgs1 helicase efficiently unwinds G-G paired DNAs. Nucleic Acids Res. 27, 1978-1984
68. Wu, X. and Maizels, N. (2001) Substrate-specific inhibition of RecQ helicase. Nucleic Acids Res. 29, 1765-1771
69. Huber, M. D., Lee, D. C. and Maizels, N. (2002) G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific inhibition. Nucleic Acids Res. 30, 3954-3961
70. Huber, M. D., Duquette, M. L., Shiels, J. C. and Maizels, N. (2006) A conserved G4 DNA binding domain in RecQ family helicases. J. Mol. Biol. 358, 1071-1080
71. Kaliraman, V. and Brill, S. J. (2002) Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae. Curr. Genet. 41, 389-400
72. Versini, G., Comet, I., Wu, M., Hoopes, L., Schwob, E. and Pasero, P. (2003) The yeast Sgs1 helicase is differentially required for genomic and ribosomal DNA replication. EMBO J. 22, 1939-1949
73. Cohen, H. and Sinclair, D. A. (2001) Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. Proc. Natl. Acad. Sci. U.S.A. 98, 3174-3179
74. Huang, P., Pryde, F. E., Lester, D., Maddison, R. L., Borts, R. H., Hickson, I. D. and Louis, E. J. (2001) SGS1 is required for telomere elongation in the absence of telomerase. Curr. Biol. 11, 125-129
75. Johnson, F. B., Marciniak, R. A., McVey, M., Stewart, S. A., Hahn, W. C. and Guarente, L. (2001) The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. EMBO J. 20, 905-913
76. Sinclair, D. A. and Guarente, L. (1997) Extrachromosomal rDNA circles: a cause of aging in yeast. Cell 91, 1033-1042
77. Sinclair, D. A., Mills, K. and Guarente, L. (1997) Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants. Science 277, 1313-1316
78. Marciniak, R. A., Lombard, D. B., Johnson, F. B. and Guarente, L. (1998) Nucleolar localization of the Werner syndrome protein in human cells. Proc. Natl. Acad. Sci. U.S.A. 95, 6887-6892
79. Crabbe, L., Verdun, R. E., Haggblom, C. I. and Karlseder, J. (2004) Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306, 1951-1953
80. n, trinucleotide repeat sequence. J. Biol. Chem. 276, 16439-16446
81. n sequences. J. Mol. Evol. 27, 96-101
82. Brosh, Jr, R. M., Majumdar, A., Desai, S., Hickson, I. D., Bohr, V. A. and Seidman, M. M. (2000) Unwinding of a DNA triple helix by the Werner and Bloom syndrome helicase. J. Biol. Chem. 276, 3024-3030
83. Yang, W. (2006) Poor base stacking at DNA lesions may initiate recognition by many repair proteins. DNA Repair 5, 654-666
84. Driscoll, H. C., Matson, S. W., Sayer, J. M., Kroth, H., Jerina, D. M. and Brosh, Jr, R. M. (2003) Inhibition of Werner syndrome helicase activity by benzo[c]phenanthrene diol epoxide dA adducts in DNA is both strand-and stereoisomer-dependent. J. Biol. Chem. 278, 41126-41135
85. Choudhary, S., Doherty, K. M., Handy, C. J., Sayer, J. M., Kroth, H., Jerina, D. M. and Brosh, Jr, R. M. (2006) Inhibition of Werner syndrome helicase activity by benzo[a]pyrene diol epoxide adducts can be overcome by replication protein A. J. Biol. Chem. 281, 6000-6009
86. Geacintov, N. E., Cosman, M., Hingerty, B. E., Amin, S., Broyde, S. and Patel, D. J. (1997) NMR solution structures of stereoisometric covalent polycyclic aromatic carcinogen-DNA adduct: principles, patterns, and diversity. Chem. Res. Toxicol. 10, 111-146
87. 6-deoxyadenosine adduct of (9S,10R)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a DNA duplex. Biochemistry 42, 1410-1420
88. 6 of deoxyadenosine. Polycyclic Aromat. Hydrocarbons 17, 95-104
89. 6-adenine adducts: unusual thermal stabilization of modified DNA duplexes. Chem. Res. Toxicol. 15, 249-261
90. Wold, M. S. (1997) Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu. Rev. Biochem. 66, 61-92
91. Shen, J. C., Gray, M. D., Oshima, J. and Loeb, L. A. (1998) Characterization of Werner syndrome protein DNA helicase activity: directionality, substrate dependence and stimulation by replication protein A. Nucleic Acids Res. 26, 2879-2885
92. Brosh, Jr, R. M., Li, J. L., Kenny, M. K., Karrow, J. K., Cooper, M. P., Kureekattil, R. P., Hickson, I. D. and Bohr, V. A. (2000) Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity. J. Biol. Chem. 275, 23500-23508
93. Shen, J. C., Lao, Y., Kamath-Loeb, A., Wold, M. S. and Loeb, L. A. (2003) The N-terminal domain of the large subunit of human replication protein A binds to Werner syndrome protein and stimulates helicase activity. Mech. Ageing Dev. 124, 921-930
94. Chen, C. Y., Graham, J. and Yan, H. (2001) Evidence for a replication function of FFA-1, the Xenopus orthologue of Werner syndrome protein. J. Cell Biol. 152, 985-996
95. Sakamoto, S., Nishikawa, K., Heo, S. J., Goto, M., Furuichi, Y. and Shimamoto, A. (2001) Werner helicase relocates into nuclear foci in response to DNA damaging agents and co-localizes with RPA and Rad51. Genes Cells 6, 421-430
96. Walpita, D., Plug, A. W., Neff, N. F., German, J. and Ashley, T. (1999) Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes. Proc. Natl. Acad. Sci. U.S.A. 96, 5622-5627
97. 6-methylguanine: implications for WRN function. DNA Repair 3, 629-638
98. Garcia, P. L., Bradley, G., Hayes, C. J., Krintel, S., Soultanas, P. and Janscak, P. (2004) RPA alleviates the inhibitory effect of vinylphosphonate internucleotide linkages on DNA unwinding by BLM and WRN helicases. Nucleic Acids Res. 32, 3771-3778
99. Machwe, A., Xiao, L., Groden, J., Matson, S. W. and Orren, D. K. (2005) RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange. J. Biol. Chem. 280, 23397-23407
100. Cheok, C. F., Wu, L., Garcia, P. L., Janscak, P. and Hickson, I. D. (2005) The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA. Nucleic Acids Res. 33, 3932-3941
101. Sugiyama, T., New, J. H. and Kowalczykowski, S. C. (1998) DNA annealing by RAD52 protein is stimulated by specific interaction with the complex of replication protein A and single-stranded DNA. Proc. Natl. Acad. Sci. U.S.A. 95, 6049-6054
102. Machwe, A., Lozada, E. M., Xiao, L. and Orren, D. K. (2006) Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins. BMC Mol. Biol. 7, 1
103. Huang, S., Li, B., Gray, M. D., Oshima, J., Mian, I. S. and Campisi, J. (1998) The premature ageing syndrome protein, WRN, is a 3′→′ exonuclease. Nat. Genet. 20, 114-116
104. Kamath-Loeb, A. S., Shen, J. C., Loeb, L. A. and Fry, M. (1998) Werner syndrome protein. II. Characterization of the integral 3′→5′ DNA exonuclease. J. Biol. Chem. 273, 34145-34150
105. Shen, J. C., Gray, M. D., Oshima, J., Kamath-Loeb, A. S., Fry, M. and Loeb, L. A. (1998) Werner syndrome protein. I. DNA helicase and DNA exonuclease reside on the same polypeptide. J. Biol. Chem. 273, 34139-34144
106. Shen, J. C. and Loeb, L. A. (2000) Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA. Nucleic Acids Res. 28, 3260-3268
107. Cooper, M. P., Machwe, A., Orren, D. K., Brosh, Jr, R. M., Ramsden, D. and Bohr, V. A. (2000) Ku complex interacts with and stimulates the Werner protein. Genes Dev. 14, 907-912
108. Harrigan, J. A., Wilson, III, D. M., Prasad, R., Opresko, P. L., Beck, G., May, A., Wilson, S. H. and Bohr, V. A. (2006) The Werner syndrome protein operates in base excision repair and cooperates with DNA polymerase β. Nucleic Acids Res. 34, 745-754
109. Albertson, T. M. and Preston, B. D. (2006) DNA replication fidelity: proofreading in trans. Curr. Biol. 16, R209-R211
110. McElhinny, S. A., Pavlov, Y. I. and Kunkel, T. A. (2006) Evidence for extrinsic exonucleolytic proofreading. Cell Cycle 5, 958-962
111. Li, B. and Comai, L. (2000) Functional interaction between Ku and the Werner syndrome protein in DNA end processing. J. Biol. Chem. 275, 28349-28352
112. Orren, D. K., Machwe, A., Karmakar, P., Piotrowski, J., Cooper, M. P. and Bohr, V. A. (2001) A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA. Nucleic Acids Res. 29, 1926-1934
113. Opresko, P. L., Laine, J. P., Brosh, Jr, R. M., Seidman, M. M. and Bohr, V. A. (2001) Coordinate action of the helicase and 3′ to 5′ exonuclease of Werner syndrome protein. J. Biol. Chem. 276, 44677-22687
114. Hartung, F. and Puchta, H. (2006) The RecQ gene family in plants. J. Plant Physiol. 163, 287-296
115. Hartung, F., Plchova, H. and Puchta, H. (2000) Molecular characterisation of RecQ homologues in Arabidopsis thaliana. Nucleic Acids Res. 28, 4275-4282
116. Plchova, H., Hartung, F. and Puchta, H. (2003) Biochemical characterization of an exonuclease from Arabidopsis thaliana reveals similarities to the DNA exonuclease of the human Werner syndrome protein. J. Biol. Chem. 278, 44128-44138
117. Li, B., Conway, N., Navarro, S., Comai, L. and Comai, L. (2005) A conserved and species-specific functional interaction between the Werner syndrome-like exonuclease atWEX and the Ku heterodimer in Arabidopsis. Nucleic Acids Res. 33, 6861-6867
118. Bachrati, C. Z. and Hickson, I. D. (2003) RecQ helicases: suppressors of tumorigenesis and premature ageing. Biochem. J. 374, 577-606
119. Cobb, J. A., Bjergbaek, L., Shimada, K., Frei, C. and Gasser, S. M. (2003) DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1. EMBO J. 22, 4325-4336
120. Cobb, J. A., Schleker, T., Rojas, V., Bjergbaek, L., Tercero, J. A. and Gasser, S. M. (2005) Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations. Genes Dev. 19, 3055-3069
121. Bjergbaek, L., Cobb, J. A., Tsai-Pflugfelder, M. and Gasser, S. M. (2005) Mechanistically distinct roles for Sgs1p in checkpoint activation and replication fork maintenance. EMBO J. 24, 405-417
122. Fricke, W. M. and Brill, S. J. (2003) Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. Genes Dev. 17, 1768-1778
123. Liao, S., Graham, J. and Yan, H. (2000) The function of Xenopus Bloom's syndrome protein homolog (xBLM) in DNA replication. Genes Dev. 14, 2570-2575
124. Li, W., Kim, S. M., Lee, J. and Dunphy, W. G. (2004) Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases. J. Cell Biol. 165, 801-812
125. Kamath-Loeb, A. S., Johansson, E., Burgers, P. M. and Loeb, L. A. (2000) Functional interaction between the Werner syndrome protein and DNA polymerase δ. Proc. Natl. Acad. Sci. U.S.A. 97, 4603-4608
126. Szekely, A. M., Chen, Y. H., Zhang, C., Oshima, J. and Weissman, S. M. (2000) Werner protein recruits DNA polymerase δ to the nucleolus. Proc. Natl. Acad. Sci. U.S.A. 97, 11365-11370
127. Sangrithi, M. N., Bernal, J. A., Madine, M., Philpott, A., Lee, J., Dunphy, W. G. and Venkitaraman, A. R. (2005) Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome. Cell 121, 887-898
128. Mann, M. B., Hodges, C. A., Barnes, E., Vogel, H., Hassold, T. J. and Luo, G. (2005) Defective sister-chromatid cohesion, aneuploidy and cancer predisposition in a mouse model of type II Rothmund-Thomson syndrome. Hum. Mol. Genet. 14, 813-625
129. Liberi, G., Maffioletti, G., Lucca, C., Chiolo, I., Baryshnikova, A., Cotta-Ramusino, C., Lopes, M., Pellicioli, A., Haber, J. E. and Foiani, M. (2005) Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase. Genes Dev. 19, 339-350
130. Ii, M. and Brill, S. J. (2005) Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae. Curr. Genet. 48, 213-225
131. Prince, P. R., Emond, M. J. and Monnat, Jr, R. J. (2001) Loss of Werner syndrome protein function promotes aberrant mitotic recombination. Genes Dev. 15, 933-938
132. Saintigny, Y., Makienko, K., Swanson, C., Emond, M. J. and Monnat, Jr, R. J. (2002) Homologous recombination resolution defect in Werner syndrome. Mol. Cell. Biol. 22, 6971-6978
133. Chen, L., Huang, S., Lee, L., Davalos, A., Schiestl, R. H., Campisi, J. and Oshima, J. (2003) WRN, the protein deficient in Werner syndrome, plays a critical structural role in optimizing DNA repair. Aging Cell 2, 191-199
134. Swanson, C., Saintigny, Y., Emond, M. J. and Monnat, Jr, R. J. (2004) The Werner syndrome protein has separable recombination and survival functions. DNA Repair 3, 475-482
135. Hope, J. C., Mense, S. M., Jalakas, M., Mitsumoto, J. and Freyer, G. A. (2006) Rqh1 blocks recombination between sister chromatids during double strand break repair, independent of its helicase activity. Proc. Natl. Acad. Sci. U.S.A. 103, 5875-5880
136. Lo, Y. C., Paffett, K. S., Amit, O., Clikeman, J. A., Sterk, R., Brenneman, M. A. and Nickoloff, J. A. (2006) Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity. Mol. Cell. Biol. 26, 4086-4094
137. Courcelle, J., Donaldson, J. R., Chow, K. H. and Courcelle, C. T. (2003) DNA damage-induced replication fork regression and processing in Escherichia coli. Science 299, 1064-1067
138. Hishida, T., Han, Y. W., Shibata, T., Kubota, Y., Ishino, Y., Iwasaki, H. and Shinagawa, H. (2004) Role of the Escherichia coli RecQ DNA helicase in SOS signaling and genome stabilization at stalled replication forks. Genes Dev. 18, 1886-1897
139. Davies, S. L., North, P. S., Dart, A., Lakin, N. D. and Hickson, I. D. (2004) Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S-phase arrest. Mol. Cell. Biol. 24, 1279-1291
140. Bischof, O., Kim, S. H., Irving, J., Beresten, S., Ellis, N. A. and Campisi, J. (2001) Regulation and localization of the Bloom syndrome protein in response to DNA damage. J. Cell Biol. 153, 367-380
141. Rodriguez-Lopez, A. M., Jackson, D. A., Iborra, F. and Cox, L. S. (2002) Asymmetry of DNA replication fork progression in Werner's syndrome. Aging Cell 1, 30-39
142. Brosh, Jr, R. M., Driscoll, H. C., Dianov, G. L. and Sommers, J. A. (2002) Biochemical characterization of the WRN-FEN-1 functional interaction. Biochemistry 41, 12204-12216
143. Brosh, Jr, R. M., von Kobbe, C., Sommers, J. A., Karmakar, P., Opresko, P. L., Piotrowski, J., Dianova, I., Dianov, G. L. and Bohr, V. A. (2001) Werner syndrome protein interacts with human Flap endonuclease 1 and stimulates its cleavage activity. EMBO J. 20, 5791-5801
144. Sharma, S., Sommers, J. A., Wu, L., Bohr, V. A., Hickson, I. D. and Brosh, Jr, R. M. (2004) Stimulation of Flap endonuclease-1 by the Bloom's syndrome protein. J. Biol. Chem. 279, 9847-9856
145. Sharma, S., Sommers, J. A., Gary, R. K., Friedrich-Heineken, E., Hubscher, U. and Brosh, Jr, R. M. (2005) The interaction site of flap endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic Acids Res. 33, 6769-6781
146. Wang, W. and Bambara, R. A. (2005) Human Bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure. J. Biol. Chem. 280, 5391-5399
147. Zheng, L., Zhou, M., Chai, Q., Parrish, J., Xue, D., Patrick, S. M., Turchi, J. T., Yannone, S. M., Chen, D. and Shen, B. (2005) Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks. EMBO Rep. 6, 83-89
148. Doherty, K. M., Sharma, S., Uzdilla, L., Wilson, T. M., Cui, S., Vindigni, A. and Brosh, Jr, R. M. (2005) RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. J. Biol. Chem. 280, 28085-28094
149. Sharma, S., Sommers, J. A., Driscoll, H. C., Uzdilla, L., Wilson, T. M. and Brosh, Jr, R. M. (2003) The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein. J. Biol. Chem. 278, 23487-23496
150. Zhang, R., Sengupta, S., Yang, Q., Linke, S. P., Yanaihara, N., Bradsher, J., Blais, V., McGowan, C. H. and Harris, C. C. (2005) BLM helicase facilitates Mus81 endonuclease activity in human cells. Cancer Res. 65, 2526-2531
151. Liu, R., Qiu, J., Finger, L. D., Zheng, L. and Shen, B. (2006) The DNA-protein interaction modes of FEN-1 with gap substrates and their implication in preventing duplication mutations. Nucleic Acids Res. 34, 1772-1784
152. Sharma, S., Sommers, J. A. and Brosh, Jr, R. M. (2004) In vivo function of the conserved non-catalytic domain of Werner syndrome helicase in DNA replication. Hum. Mol. Genet. 13, 2247-2261
153. Imamura, O. and Campbell, J. L. (2003) The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants. Proc. Natl. Acad. Sci. U.S.A. 100, 8193-8198
154. Harmon, F. G., DiGate, R. J. and Kowalczykowski, S. C. (1999) RecQ helicase and topoisomerase III comprise a novel DNA strand passage function: a conserved mechanism for control of DNA recombination. Mol. Cell 3, 611-620
155. Harmon, F. G., Brockman, J. P. and Kowalczykowski, S. C. (2003) RecQ helicase stimulates both DNA catenation and changes in DNA topology by topoisomerase III. J. Biol. Chem. 278, 42668-42678
156. Bennett, R. J. and Wang, J. C. (2001) Association of yeast DNA topoisomerase III and Sgs1 DNA helicase: studies of fusion proteins. Proc. Natl. Acad. Sci. U.S.A. 98, 11108-11113
157. Fricke, W. M., Kaliraman, V. and Brill, S. J. (2001) Mapping the DNA topoisomerase III binding domain of the Sgs1 DNA helicase. J. Biol. Chem. 276, 8848-8855
158. Gangloff, S., McDonald, J. P., Bendixen, C., Arthur, L. and Rothstein, R. (1994) The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol. Cell. Biol. 14, 8391-8398
159. Ira, G., Malkova, A., Liberi, G., Foiani, M. and Haber, J. E. (2003) Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell 115, 401-411
160. Mankouri, H. W. and Hickson, I. D. (2004) Understanding the rales of RecQ helicases in the maintenance of genome integrity and suppression of tumorigenesis. Biochem. Soc. Trans. 32, 957-958
161. 2. Mol. Cell. Biol. 23, 3692-3705
162. Ahn, J. S., Osman, F. and Whitby, M. C. (2005) Replication fork blockage by RTS1 at an ectopic site promotes recombination in fission yeast. EMBO J. 24, 2011-2023
163. Win, T. Z., Mankouri, H. W., Hickson, I. D. and Wang, S. W. (2005) A role for the fission yeast Rqh1 helicase in chromosome segregation. J. Cell Sci. 118, 5777-5784
164. Hu, P., Beresten, S. F., van Brabant, A. J., Ye, T. Z., Pandolfi, P. P., Johnson, F. B., Guarente, L. and Ellis, N. A. (2001) Evidence for BLM and topoisomerase IIIα interaction in genomic stability. Hum. Mol. Genet. 10, 1287-1298
165. Johnson, F. B., Lombard, D. B., Neff, N. F., Mastrangelo, M. A., Dewolf, W., Ellis, N. A., Marciniak, R. A., Yin, Y., Jaenisch, R. and Guarente, L. (2000) Association of the Bloom syndrome protein with topoisomerase IIIα in somatic and meiotic cells. Cancer Res. 60, 1162-1167
166. Wu, L., Davies, S. L., North, P. S., Goulaouic, H., Riou, J. F., Turley, H., Gatter, K. C. and Hickson, I. D. (2000) The Bloom's syndrome gene product interacts with topoisomerase III. J. Biol. Chem. 275, 9636-9644
167. Wu, L. and Hickson, I. D. (2002) The Bloom's syndrome helicase stimulates the activity of human topoisomerase IIIα. Nucleic Acids Res. 30, 4823-4829
168. Chang, M., Bellaoui, M., Zhang, C., Desai, R., Morozov, P., Delgado-Cruzata, L., Rothstein, R., Freyer, G. A., Boone, C. and Brown, G. W. (2005) RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. EMBO J. 24, 2024-2033
169. Mullen, J. R., Nallaseth, F. S., Lan, Y. Q., Slagle, C. E. and Brill, S. J. (2005) Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mol. Cell. Biol. 25, 4476-4487
170. Yin, J., Sobeck, A., Xu, C., Meetei, A. R., Hoatlin, M., Li, L. and Wang, W. (2005) BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J. 24, 1465-1476
171. Wu, L. and Hickson, I. D. (2003) The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature (London) 426, 870-874
172. Raynard, S., Bussen, W. and Sung, P. (2006) A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIα, and BLAP75. J. Biol. Chem. 281, 13861-13864
173. Wu, L., Bachrati, C. Z., Ou, J., Xu, C., Yin, J., Chang, M., Wang, W., Li, L., Brown, G. W. and Hickson, I. D. (2006) BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc. Natl. Acad. Sci. U.S.A. 103, 4068-4073
174. Shimamoto, A., Nishikawa, K., Kitao, S. and Furuichi, Y. (2000) Human RecQ5β, a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerases 3α and 3β. Nucleic Acids Res. 28, 1647-1655
175. Wang, W., Seki, M., Narita, Y., Nakagawa, T., Yoshimura, A., Otsuki, M., Kawabe, Y., Tada, S., Yagi, H., Ishii, Y. and Enomoto, T. (2003) Functional relation among RecQ family helicases RecQL1, RecQL5, and BLM in cell growth and sister chromatid exchange formation. Mol. Cell. Biol. 23, 3527-3535
176. Hu, Y., Lu, X., Barnes, E., Yan, M., Lou, H. and Luo, G. (2005) Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers. Mol. Cell. Biol. 25, 3431-3442
177. Cahill, D., Connor, B. and Carney, J. P. (2006) Mechanisms of eukaryotic DNA double strand break repair. Front. Biosci. 11, 1958-1976
178. Karmakar, P., Snowden, C. M., Ramsden, D. A. and Bohr, V. A. (2002) Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus. Nucleic Acids Res. 30, 3583-3591
179. Li, B. and Comai, L. (2001) Requirements for the nucleolytic processing of DNA ends by the Werner syndrome protein-Ku70/80 complex. J. Biol. Chem. 276, 9896-9902
180. Karmakar, P., Piotrowski, J., Brosh, Jr, R. M., Sommers, J. A., Miller, S. P., Cheng, W. H., Snowden, C. M., Ramsden, D. A. and Bohr, V. A. (2002) Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation. J. Biol. Chem. 277, 18291-18302
181. Yannone, S. M., Roy, S., Chan, D. W., Murphy, M. B., Huang, S., Campisi, J. and Chen, D. J. (2001) Werner syndrome protein is regulated and phosphorylated by DNA-dependent protein kinase. J. Biol. Chem. 276, 38242-38248
182. Oshima, J., Huang, S., Pae, C., Campisi, J. and Schiestl, R. H. (2002) Lack of WRN results in extensive deletion at nonhomologous joining ends. Cancer Res. 62, 547-551
183. Gaymes, T. J., North, P. S., Brady, N., Hickson, I. D., Mufti, G. J. and Rassool, F. V. (2002) Increased error-prone non homologous DNA end-joining: a proposed mechanism of chromosomal instability in Bloom's syndrome. Oncogene 21, 2525-2533
184. Langland, G., Elliott, J., Li, Y., Creaney, J., Dixon, K. and Groden, J. (2002) The BLM helicase is necessary for normal DNA double-strand break repair. Cancer Res. 62, 2766-2770
185. Runger, T. M. and Kraemer, K. H. (1989) Joining of linear plasmid DNA is reduced and error-prone in Bloom's syndrome cells. EMBO J. 8, 1419-1425
186. Kusano, K., Johnson-Schlitz, D. M. and Engels, W. R. (2001) Sterility of Drosophila with mutations in the Bloom syndrome gene: complementation by Ku70. Science 291, 2600-2602
187. Min, B., Weinert, B. T. and Rio, D. C. (2004) Interplay between Drosophila Bloom's syndrome helicase and Ku autoantigen during nonhomologous end joining repair of P element-induced DNA breaks. Proc. Natl. Acad. Sci. U.S.A. 101, 8906-8911
188. Adams, M. D., McVey, M. and Sekelsky, J. J. (2003) Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing. Science 299, 265-267
189. McVey, M., Adams, M., Staeva-Vieira, E. and Sekelsky, J. J. (2004) Evidence for multiple cycles of strand invasion during repair of double-strand gaps in Drosophila. Genetics 167, 699-705
190. Yan, H., McCane, J., Toczylowski, T. and Chen, C. (2005) Analysis of the Xenopus Werner syndrome protein in DNA double-strand break repair. J. Cell Biol. 171, 217-227
191. Cheng, W. H., von Kobbe, C., Opresko, P. L., Arthur, L. M., Komatsu, K., Seidman, M. M., Carney, J. P. and Bohr, V. A. (2004) Linkage between Werner syndrome protein and the Mre11 complex via Nbs1. J. Biol. Chem. 279, 21169-21176
192. Baynton, K., Otterlei, M., Bjoras, M., von Kobbe, C., Bohr, V. A. and Seeberg, E. (2003) WRN interacts physically and functionally with the recombination mediator protein RAD52. J. Biol. Chem. 278, 36476-36486
193. Lan, L., Nakajima, S., Komatsu, K., Nussenzweig, A., Shimamoto, A., Oshima, J. and Yasui, A. (2005) Accumulation of Werner protein at DNA double-strand breaks in human cells. J. Cell Sci. 118, 4153-4162
194. Zhang, N., Kaur, R., Lu, X., Shen, X., Li, L. and Legerski, R. J. (2005) The Pso4 mRNA splicing and DNA repair complex interacts with WRN for processing of DNA interstrand cross-links. J. Biol. Chem. 280, 40559-40567
195. Wu, L., Davies, S. L., Levitt, N. C. and Hickson, I. D. (2001) Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. J. Biol. Chem. 276, 19375-19381
196. Braybrooke, J. P., Li, J. L., Wu, L., Caple, F., Benson, F. E. and Hickson, I. D. (2003) Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D). J. Biol. Chem. 278, 48357-48366
197. Sengupta, S., Robles, A. I., Linke, S. P., Sinogeeva, N. I., Zhang, R., Pedeux, R., Ward, I. M., Celeste, A., Nussenzweig, A., Chen, J. et al. (2004) Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J. Cell Biol. 166, 801-813
198. Myung, K., Datta, A., Chen, C. and Kolodner, R. D. (2001) SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination. Nat. Genet. 27, 113-116
199. Sugawara, N., Goldfarb, T., Studamire, B., Alani, E. and Haber, J. E. (2004) Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1. Proc. Natl. Acad. Sci. U.S.A. 101, 9315-9320
200. Cobb, J., Bjergbaek, L. and Gasser, S. (2002) RecQ helicases: at the heart of genetic stability. FEBS Lett. 529, 43-48
201. Spell, R. M. and Jinks-Robertson, S. (2004) Examination of the roles of Sgs1 and Srs2 helicases in the enforcement of recombination fidelity in Saccharomyces cerevisiae. Genetics 168, 1855-1865
202. Onoda, F., Seki, M., Wang, W. and Enomoto, T. (2004) The hyper unequal sister chromatid recombination in an sgs1 mutant of budding yeast requires MSH2. DNA Repair 3, 1355-1362
203. Goldfarb, T. and Alani, E. (2004) Distinct roles for the Saccharomyces cerevisiae mismatch repair proteins in heteroduplex rejection, mismatch repair, and non-homologous tail removal. Genetics 169, 563-574
204. Pedrazzi, G., Perrera, C., Blaser, H., Kuster, P., Marra, G., Davies, S. L., Ryu, G.-H., Freire, R., Hickson, I. D., Jiricny, J. and Stagljar, I. (2001) Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1. Nucleic Acids Res. 29, 4378-4386
205. Pedrazzi, G., Bachrati, C. Z., Selak, N., Studer, I., Petkovic, M., Hickson, I. D., Jiricny, J. and Stagljar, I. (2003) The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6. Biol. Chem. 384, 1155-1164
206. Langland, G., Kordich, J., Creaney, J., Goss, K. H., Lillard-Wetherell, K., Bebenek, K., Kunkel, T. A. and Groden, J. (2001) The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair. J. Biol. Chem. 276, 30031-30035
207. Yang, Q., Zhang, R., Wang, X. W., Linke, S. P., Sengupta, S., Hickson, I. D., Pedrazzi, G., Perrera, C., Stagljar, I., Littman, S. J. et al. (2004) The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase. Oncogene 23, 3749-3756
208. Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J. and Qin, J. (2000) BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 14, 927-939
209. Surtees, J. A., Argueso, J. L. and Alani, E. (2004) Mismatch repair proteins: key regulators of genetic recombination. Cytogenet. Genome Res. 107, 146-159
210. Harrigan, J. A., Opresko, P. L., von Kobbe, C., Kedar, P. S., Prasad, R., Wilson, S. H. and Bohr, V. A. (2003) The Werner syndrome protein stimulates DNA polymerase β strand displacement synthesis via its helicase activity. J. Biol. Chem. 278, 22686-22695
211. Ahn, B., Harrigan, J. A., Indig, F. E., Wilson, III, D. M. and Bohr, V. A. (2004) Regulation of WRN helicase activity in human base excision repair. J. Biol. Chem. 279, 53465-53474
212. Szekely, A. M., Bleichert, F., Numann, A., Van Komen, S., Manasanch, E., Ben Nasr, A., Canaan, A. and Weissman, S. M. (2005) Werner protein protects nonproliferating cells from oxidative DNA damage. Mol. Cell. Biol. 25, 10492-10506
213. von Kobbe, C., Harrigan, J. A., May, A., Opresko, P. L., Dawut, L., Cheng, W. H. and Bohr, V. A. (2003) Central role for the Werner syndrome protein/poly(ADP-ribose) polymerase 1 complex in the poly(ADP-ribosyl)ation pathway after DNA damage. Mol. Cell. Biol. 23, 8601-8613
214. von Kobbe, C., Harrigan, J. A., Schreiber, V., Stiegler, P., Piotrowski, J., Dawut, L. and Bohr, V. A. (2004) Poly(ADP-ribose) polymerase 1 regulates both the exonuclease and helicase activities of the Werner syndrome protein. Nucleic Acids Res. 32, 4003-4014
215. Deschenes, F., Massip, L., Garanti, C. and Lebel, M. (2005) In vivo misregulation of genes involved in apoptosis, development and oxidative stress in mice lacking both functional Werner syndrome protein and poly(ADP-ribose) polymerase-1. Hum. Mol. Genet. 14, 3293-3308
216. Azam, M., Lee, J. Y., Abraham, V., Chanoux, R., Schoenly, K. A. and Johnson, F. B. (2006) Evidence that the S cerevisiae. Sgs1 protein facilitates recombinational repair of telomeres during senescence. Nucleic Acids Res. 34, 506-516
217. Stavropoulos, D. J., Bradshaw, P. S., Li, X., Pasic, I., Truong, K., Ikura, M., Ungrin, M. and Meyn, M. S. (2002) The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis. Hum. Mol. Genet. 11, 3135-3144
218. Lillard-Wetherell, K., Machwe, A., Langland, G. T., Combs, K. A., Behbehani, G. K., Schonberg, S. A., German, J., Turchi, J. J., Orren, D. K. and Groden, J. (2004) Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2. Hum. Mol. Genet. 13, 1919-1932
219. Opresko, P. L., von Kobbe, C., Laine, J. P., Harrigan, J., Hickson, I. D. and Bohr, V. A. (2002) Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J. Biol. Chem. 277, 41110-41119
220. Lillard-Wetherell, K., Combs, K. A. and Groden, J. (2005) BLM helicase complements disrupted type II telomere lengthening in telomerase-negative sgs1 yeast. Cancer Res. 65, 5520-5522
221. Davis, T., Singhrao, S. K., Wyllie, F. S., Haughton, M. F., Smith, P. J., Wiltshire, M., Wynford-Thomas, D., Jones, C. J., Faragher, R. G. and Kipling, D. (2003) Telomere-based proliferative lifespan barriers in Werner-syndrome fibroblasts involve both p53-dependent and p53-independent mechanisms. J. Cell Sci. 116, 1349-1357
222. Schulz, V. P., Zakian, V. A., Ogburn, C. E., McKay, J., Jarzebowicz, A. A., Martin, G. M. and Edland, S. D. (1996) Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells. Hum. Genet. 97, 750-754
223. Tahara, H., Tokutake, Y., Maeda, S., Kataoka, H., Watanabe, T., Satoh, M., Matsumoto, T., Sugawara, M., Ide, T., Goto, M. et al. (1997) Abnormal telomere dynamics of B-lymphoblastoid cell strains from Werner's syndrome patients transformed by Epstein-Barr virus. Oncogene 15, 1911-1920
224. Wyllie, F. S., Jones, C. J., Skinner, J. W., Haughton, M. F., Wallis, C., Wynford-Thomas, D., Faragher, R. G. and Kipling, D. (2000) Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts. Nat. Genet. 24, 16-17
225. Du, X., Shen, J., Kugan, N., Furth, E. E., Lombard, D. B., Cheung, C., Pak, S., Luo, G., Pignolo, R. J., DePinho, R. A. et al. (2004) Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol. Cell. Biol. 24, 8437-8446
226. Bai, Y. and Murnane, J. P. (2003) Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein. Hum. Genet. 113, 337-347
227. Hickson, I. D. (2003) RecQ helicases: caretakers of the genome. Nat. Rev. Cancer 3, 169-178
228. Schawalder, J., Paric, E. and Neff, N. F. (2003) Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase. BMC Cell Biol. 4, 15
229. Machwe, A., Xiao, L. and Orren, D. K. (2004) TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA. Oncogene 23, 149-156
230. Opresko, P. L., Mason, P. A., Podell, E. R., Lei, M., Hickson, I. D., Cech, T. R. and Bohr, V. A. (2005) POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. J. Biol. Chem. 280, 32069-32080
231. Chang, S., Multani, A. S., Cabrera, N. G., Naylor, M. L., Laud, P., Lombard, D., Pathak, S., Guarente, L. and DePinho, R. A. (2004) Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat. Genet. 36, 877-882
232. Laud, P. R., Multani, A. S., Bailey, S. M., Wu, L., Ma, J., Kingsley, C., Lebel, M., Pathak, S., DePinho, R. A. and Chang, S. (2005) Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes Dev. 19, 2560-2570
233. Chang, S. (2005) A mouse model of Werner Syndrome: what can it tell us about aging and cancer? Int. J. Biochem. Cell Biol. 37, 991-999
234. von Kobbe, C., Karmakar, P., Dawut, L., Opresko, P. L., Zeng, X., Brosh, Jr, R. M., Hickson, I. D. and Bohr, V. A. (2002) Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins. J. Biol. Chem. 277, 22035-22044
235. Sharma, S., Doherty, K. M. and Brosh, Jr, R. M. (2005) DNA helicases as targets for anti-cancer drugs. Curr. Med. Chem. Anticancer Agents 5, 183-199
236. Grandori, C., Wu, K. J., Fernandez, P., Ngouenet, C., Grim, J., Clurman, B. E., Moser, M. J., Oshima, J., Russell, D. W., Swisshelm, K. et al. (2003) Werner syndrome protein limits MYC-induced cellular senescence. Genes Dev. 17, 1569-1574
237. Grandori, C., Robinson, K. L., Galloway, D. A. and Swisshelm, K. (2004) Functional link between Myc and the Werner gene in tumorigenesis. Cell Cycle 3, 22-25
238. Doherty, K. M., Sharma, S., Gupta, R. and Brosh, Jr, R. M. (2006) Tetraplex binding molecules as anti-cancer agents. Recent Pat. Anti-Cancer Drug Discov. 1, 185-200
239. Han, H., Langley, D. R., Rangan, A. and Hurley, L. H. (2001) Selective interactions of cationic porphyrins with G-quadruplex structures. J. Am. Chem. Soc. 123, 8902-8913
240. Li, J. L., Harrison, R. J., Reszk, A. P., Brosh, Jr, R. M., Bohr, V. A., Neidle, S. and Hickson, I. D. (2001) Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands. Biochemistry 40, 15194-15202
241. Morita, H., Kurihara, H., Sugiyama, T., Hamada, C. and Yazaki, Y. (1999) A polymorphic variant C1367R of the Werner helicase gene and atherosclerotic diseases in the Japanese population. Thromb. Haemostasis 82, 160-161
242. Ye, L., Miki, T., Nakura, J., Oshima, J., Kamino, K., Rakugi, H., Ikegami, H., Higaki, J., Edland, S. D., Martin, G. M. and Ogihara, T. (1997) Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population. Am. J. Med. Genet. 68, 494-498
243. Bohr, V. A., Metter, E. J., Harrigan, J. A., von Kobbe, C., Liu, J. L., Gray, M. D., Majumdar, A., Wilson, III, D. M. and Seidman, M. M. (2004) Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients. Mech. Ageing Dev. 125, 491-496
244. Kamath-Loeb, A. S., Welcsh, P., Waite, M., Adman, E. T. and Loeb, L. A. (2004) The enzymatic activities of the Werner syndrome protein are disabled by the amino acid polymorphism R834C. J. Biol. Chem. 279, 55499-55505
245. Kuningas, M., Slagboom, P. E., Westendorp, R. G. and van Heemst, D. (2006) Impact of genetic variations in the WRN gene on age related pathologies and mortality. Mech. Ageing Dev. 127, 307-313
246. Bendixen, M. H., Nexo, B. A., Bohr, V. A., Frederiksen, H., McGue, M., Kolvraa, S. and Christensen, K. (2004) A polymorphic marker in the first intron of the Werner gene associates with cognitive function in aged Danish twins. Exp. Gerontol. 39, 1101-1107
247. Payao, S. L., de Labio, R. W., Gatti, L. L., Rigolin, V. O., Bertolucci, P. H. and Smith, M. A. (2004) Werner helicase polymorphism is not associated with Alzheimer's disease. J. Alzheimers Dis. 6, 591-594
248. Smith, M. A., Silva, M. D., Araujo, L. Q., Ramos, L. R., Labio, R. W., Burbano, R. R., Peres, C. A., Andreoli, S. B., Payao, S. L. and Cendoroglo, M. S. (2005) Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population. Braz. J. Med. Biol. Res. 38, 1053-1059
249. Wirtenberger, M., Frank, B., Hemminki, K., Klaes, R., Schmutzler, R. K., Wappenschmidt, B., Meindl, A., Kiechle, M., Arnold, N., Weber, B. H. et al. (2006) Interaction of Werner and Bloom syndrome genes with p53 in familial breast cancer. Carcinogenesis, doi:10.1093/carcin/bgl067
250. Blander, G., Kipnis, J., Leal, J. F., Yu, C. E., Schellenberg, G. D. and Oren, M. (1999) Physical and functional interaction between p53 and the Werner's syndrome protein. J. Biol. Chem. 274, 29463-29469
251. Brosh Jr, R. M., Karmakar, P., Sommers, J. A., Yang, Q., Wang, X. W., Spillare, E. A., Harris, C. C. and Bohr, V. A. (2001) p53 modulates the exonuclease activity of Werner syndrome protein. J. Biol. Chem. 276, 35093-35102
252. Sengupta, S., Linke, S. P., Pedeux, R., Yang, Q., Farnsworth, J., Garfield, S. H., Valerie, K., Shay, J. W., Ellis, N. A., Wasylyk, B. and Harris, C. C. (2003) BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination. EMBO J. 22, 1210-1222
253. Sommers, J. A., Sharma, S., Doherty, K. M., Karmakar, P., Yang, Q., Kenny, M. K., Harris, C. C. and Brosh, Jr, R. M. (2005) p53 modulates RPA-dependent and RPA-independent WRN helicase activity. Cancer Res. 65, 1223-1233
254. Spillare, E. A., Robles, A. I., Wang, X. W., Shen, J. C., Yu, C. E., Schellenberg, G. D. and Harris, C. C. (1999) p53-mediated apoptosis is attenuated in Werner syndrome cells. Genes Dev. 13, 1355-1360
255. Yang, Q., Znang, R., Wang, X. W., Spillare, E. A., Linke, S. P., Subramanian, D., Griffith, J. D., Li, J. L., Hickson, I. D., Shen, J. C. et al. (2002) The processing of Holliday junctions by BLM and WRN helicases is regulated by p53. J. Biol. Chem. 277, 31980-31987
256. Spillare, E. A., Wang, X. W., von Kobbe, C., Bohr, V. A., Hickson, I. D. and Harris, C. C. (2005) Redundancy of DNA helicases in p53-mediated apoptosis. Oncogene 25, 2119-2123
257. Wang, X. W., Tseng, A., Ellis, N. A., Spillare, E. A., Linke, S. P., Robles, A. I., Seker, H., Yang, Q., Hu, P., Beresten, S. et al. (2001) Functional interaction of p53 and BLM DNA helicase in apoptosis. J. Biol. Chem. 276, 32948-32955
258. Moser, M. J., Kamath-Loeb, A. S., Jacob, J. E., Bennett, S. E., Oshima, J. and Monnat, Jr, R. J. (2000) WRN helicase expression in Werner syndrome cell lines. Nucleic Acids Res. 28, 648-654
259. Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, A., Hanson, N. B., Martin, G. M. et al. (2003) LMNA mutations in atypical Werner's syndrome. Lancet 362, 440-445
260. Li, D., Frazier, M., Evans, D. B., Hess, K. R., Crane, C. H., Jiao, L. and Abbruzzese, J. L. (2006) Single nucleotide polymorphisms of RecQ1, RAD54L and ATM genes are associated with reduced survival of pancreatic cancer. J. Clin. Oncol. 24, 1720-1728
261. Li, D., Liu, H., Jiao, L., Chang, D. Z., Beinart, G., Wolff, R. A., Evans, D. B., Hassan, M. M. and Abbruzzese, J. L. (2006) Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival. Cancer Res. 66, 3323-3330
262. Ooi, S. L., Shoemaker, D. D. and Boeke, J. D. (2003) DNA helicase gene interaction network defined using synthetic lethality analyzed by microarray. Nat. Genet. 35, 277-286
263. Schmidt, K. H. and Kolodner, R. D. (2004) Requirement of Rrm3 helicase for repair of spontaneous DNA lesions in cells lacking Srs2 or Sgs1 helicase. Mol. Cell. Biol. 24, 3213-3226
264. Budd, M. E., Tong, A. H., Polaczek, P., Peng, X., Boone, C. and Campbell, J. L. (2005) A network of multi-tasking proteins at the DNA replication fork preserves genome stability. PLoS Genet. 1, e61
265. Cantor, S. B., Bell, D. W., Ganesan, S., Kass, E. M., Drapkin, R., Grossman, S., Wahrer, D. C., Sgroi, D. C., Lane, W. S., Haber, D. A. and Livingston, D. M. (2001) BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell 105, 149-160
266. Thompson, L. H. (2005) Unraveling the Fanconi anemia-DNA repair connection. Nat. Genet. 37, 921-922
267. Menichini, P. and Linial, M. (2001) SUVi and BACH1: a new subfamily of mammalian helicases? Mutat. Res. 487, 67-71
268. Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E. and Wang, W. (2003) A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Mol. Cell Biol. 23, 3417-3426
269. Pichierri, P., Franchitto, A. and Rosselli, F. (2004) BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks. EMBO J. 23, 3154-3163
270. Jiao, R., Bachrati, C. Z., Pedrazzi, G., Kuster, P., Petkovic, M., Li, J. L., Egli, D., Hickson, I. D. and Stagljar, I. (2004) Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1. Mol. Cell. Biol. 24, 4710-4719
271. Ishov, A. M., Sotnikov, A. G., Negorev, D., Vladimirova, O. V., Neff, N., Kamitani, T., Yeh, E. T., Strauss, III, J. F. and Maul, G. G. (1999) PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J. Cell Biol. 147, 221-234
272. Cheng, W. H., von Kobbe, C., Opresko, P. L., Fields, K. M., Ren, J., Kufe, D. and Bohr, V. A. (2003) Werner syndrome protein phosphorylation by abl tyrosine kinase regulates its activity and distribution. Mol. Cell. Biol. 23, 6385-6395
273. Li, B., Navarro, S., Kasahara, N. and Comai, L. (2004) Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1. J. Biol. Chem. 279, 13659-13667
274. Huang, S., Beresten, S., Li, B., Oshima, J., Ellis, N. A. and Campisi, J. (2000) Characterization of the human and mouse WRN 3′→5′ exonuclease. Nucleic Acids Res. 28, 2396-2405
275. Lebel, M., Spillare, E. A., Harris, C. C. and Leder, P. (1999) The Werner syndrome gene product co-purifies with the DNA replication complex and interacts with PCNA and topoisomerase I. J. Biol. Chem. 274, 37795-37799
276. Rodriguez-Lopez, A. M., Jackson, D. A., Nehlin, J. O., Iborra, F., Warren, A. V. and Cox, L. S. (2003) Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA. Mech. Ageing Dev. 124, 167-174
277. Nguyen, D. T., Rovira, I. I. and Finkel, T. (2002) Regulation of the Werner helicase through a direct interaction with a subunit of protein kinase A. FEBS Lett. 521, 170-174
278. Kawabe, Y., Seki, M., Seki, T., Wang, W.-S., Imamura, O., Furuichi, Y., Saitoh, H. and Enomoto, T. (2000) Covalent modification of the Werner's syndrome gene product with the ubiquitin-related protein, SUMO-1. J. Biol. Chem. 275, 20963-20966
279. Laine, J. P., Opresko, P. L., Indig, F. E., Harrigan, J. A., von Kobbe, C. and Bohr, V. A. (2003) Werner protein stimulates topoisomerase I DNA relaxation activity. Cancer Res. 63, 7136-7146
280. Partridge, J. J., Lopreiato, Jr, J. O., Latterich, M. and Indig, F. E. (2003) DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP. Mol. Biol. Cell 14, 4221-4229
281. Kawabe, Y., Branzei, D., Hayashi, T., Suzuki, H., Masuko, T., Onoda, F., Heo, S. J., Ikeda, H., Shimamoto, A., Furuichi, Y. et al. (2001) A novel protein interacts with the Werner's syndrome gene product physically and functionally. J. Biol. Chem. 276, 20364-20369
282. Petkovic, M., Dietschy, T., Freire, R., Jiao, R. and Stagljar, I. (2005) The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. J. Cell Sci. 118, 4261-4269
283. Yin, J., Tae, K. Y., Varshavsky, A. and Wang, W. (2004) RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. Hum. Mol. Genet. 13, 2421-2430
284. Seki, T., Tada, S., Katada, T. and Enomoto, T. (1997) Cloning of a cDNA encoding a novel importin-α homologue, Qip1: discrimination of Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase Q1/RecQL. Biochem. Biophys. Res. Commun. 234, 48-53
285. Cui, S., Klima, R., Ochem, A., Arosio, D., Falaschi, A. and Vindigni, A. (2003) Characterization of the DNA-unwinding activity of human RECQ1, a helicase specifically stimulated by human replication protein A. J. Biol. Chem. 278, 1424-1432