Uracil-DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of base excision repair by distinct mechanisms

Nucleic Acids Research

Volumn 35, Issue 12, 2007, Pages 3879-3892

  Pettersen, Henrik Sahlin ^a   Sundheim, Ottar ^a   Gilljam, Karin Margaretha ^a   Slupphaug, Geir ^a   Krokan, Hans Einar ^a   Kavli, Bodil ^a  

^a NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOSINE; DNA; DNA (APURINIC OR APYRIMIDINIC SITE) LYASE; RNA POLYMERASE II; URACIL; URACIL DNA GLYCOSIDASE; CCNU PROTEIN, HUMAN; DNA GLYCOSYLTRANSFERASE; SMUG1 PROTEIN, HUMAN; UNCLASSIFIED DRUG;

APURINIC SITE; APYRIMIDINIC SITE; ARTICLE; BACTERIAL CELL; BINDING AFFINITY; CELL PROLIFERATION; CHROMATIN; CONTROLLED STUDY; DEAMINATION; DNA CLEAVAGE; DNA REPLICATION; ENZYME BINDING; ESCHERICHIA COLI; EXCISION REPAIR; GENE MUTATION; IN VITRO STUDY; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN FAMILY; VERTEBRATE; AMINO ACID SUBSTITUTION; BASE MISPAIRING; BINDING SITE; CHEMISTRY; DNA REPAIR; ENZYME SPECIFICITY; ENZYMOLOGY; EUKARYOTIC CELL; GENETIC COMPLEMENTATION; GENETICS; HUMAN; METABOLISM; PROKARYOTIC CELL; PROTEIN MOTIF; SEQUENCE HOMOLOGY;

ESCHERICHIA COLI; VERTEBRATA;

AMINO ACID MOTIFS; AMINO ACID SUBSTITUTION; BASE PAIR MISMATCH; BINDING SITES; DNA GLYCOSYLASES; DNA REPAIR; DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE; ESCHERICHIA COLI; EUKARYOTIC CELLS; GENETIC COMPLEMENTATION TEST; HUMANS; PROKARYOTIC CELLS; SEQUENCE HOMOLOGY, AMINO ACID; SUBSTRATE SPECIFICITY; URACIL-DNA GLYCOSIDASE;

EID: 34547645005     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkm372     Document Type: Article

References (56)

1. Lindahl,T. (1993) Instability and decay of the primary structure of DNA. Nature, 362, 709-715.
2. Barnes,D.E. and Lindahl,T. (2004) Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu. Rev. Genet., 38, 445-476.
3. Lari,S.U., Chen,C.Y., Vertessy,B.G., Morre,J. and Bennett,S.E. (2006) Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance. DNA Repair (Amst.), 5, 1407-1420.
4. Neuberger,M.S., Harris,R.S.,.Di Noia,J. and Petersen-Mahrt,S.K. (2003) Immunity through DNA deamination. Trends Biochem. Sci., 28, 305-312.
5. Guillet,M. and Boiteux,S. (2003).Origin of endogenous DNA basic sites in Saccharomyces cerevisiae. Mol. Cell. Biol., 23, 8386-8394.
6. NilsenH., Haushalter,K.A., Robins,P., Barnes,D.E., Verdine,G.L. and Lindahl,T. (2001) Excision of deaminated cytosine from the vertebrate genome: Role of the SMUG1 uracil-DNA glycosylase. EMBO J., 20 4278-4286.
7. Kavli,B., Sundheim,O., Akbari,M., Otterlei,M., Nilsen,H., Skorpen,F., Aas,P.A., Hagen,L., Krokan,H.E. et al. (2002) hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. J. Biol. Chem., 277, 39926-39936.
8. An,Q., Robins,P., Lindahl,T. and Barnes,D.E. (2005) C → T mutagenesis and gamma-radiation sensitivity due to deficiency in the Smug1 and Ung DNA glycosylases. EMBO J., 24, 2205-2213.
9. Nilsen,H., Rosewell,I., Robins,P., Skjelbred,C.F., Andersen,S., Slupphaug,G., Daly,G., Krokan,H.E., Lindahl,T. et al. (2000) Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. Mol. Cell., 5, 1059-1065.
10. Kavli,B., Andersen,S., Otterlei,M., Liabakk,N.B., Imai,K., Fischer,A., Durandy,A., Krokan,H.E. and Slupphaug,G. (2005) B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. J. Exp. Med., 201, 2011-2021.
11. Di Noia,J.M., Rada,C. and Neuberger,M.S. (2006) SMUG1 is able to excise uracil from immunoglobulin genes: Insight into mutation versus repair. EMBO J., 25, 585-595.
12. Nagelhus,T.A., Haug,T., Singh,K.K., Keshav,K.F., Skorpen,F., Otterlei,M., Bharati,S., Lindmo,T., Benichou,S. et al. (1997) A sequence in the N-terminal region of human uracil-DNA glycosylase with homology to XPA interacts with the C-terminal part of the 34-kDa subunit of replication protein A. J. Biol. Chem., 272, 6561-6566.
13. Otterlei,M., Warbrick,E., Nagelhus,T.A., Haug,T., Slupphaug,G., Akbari,M., Aas,P.A., Steinsbekk,K., Bakke,O. et al. (1999) Post-replicative base excision repair in replication foci. EMBO J. 18, 3834-3844.
14. Slupphaug,G., Olsen,L.C., Helland,D., Aasland,R. and Krokan,H.E. (1991) Cell cycle regulation and in vitro hybrid arrest analysis of the major human uracil-DNA glycosylase. Nucleic Acids Res., 19, 5131-5137.
15. Haug,T., Skorpen,F., Aas,P.A., Malm,V., Skjelbred,C. and Krokan,H.E. (1998) Regulation of expression of nuclear and mitochondrial forms of human uracil-DNA glycosylase. Nucleic Acids Res., 26, 1449-1457.
16. Boorstein,R.J., Cununings,A.Jr, Marenstein,D.R., Chan,M.K., Ma,Y., Neubert,T.A., Brown,S.M. and Teebor,G.W. (2001) Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1. J. Biol. Chem., 276, 41991-41997.
17. Aravind,L. and Koonin,E.V. (2000) The alpha/beta fold uracil DNA glycosylases: A common origin with diverse fates. Genome Biol., 1, RESEARCH0007.
18. Wibley,J.E., Waters,T.R., Haushalter,K., Verdine,G.L. and Pearl,L.H. (2003) Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1. Mol. Cell, 11, 1647-1659.
19. Blatny,J.M., Brautaset,T., Winther-Latsen,H.C., Karunakaran,P. and Valla,S. (1997) Improved broad-host-range RK2 vectors useful for high and low regulated gene expression levels in gram-negative bacteria. Plasmid, 38, 35-51.
20. Scaramozzino,N., Sanz,G., Crance,J.M., Saparbaev,M., Drillien,R., Laval,J., Kavli,B. and Garin,D. (2003) Characterisation of the substrate specificity of homogeneous vaccinia virus uracil-DNA glycosylase. Nucleic Acids Res., 31, 4950-457.
21. Rothwell,D.G., Hang,B., Gorman,M.A., Freemont,P.S., Singer,B. and Hickson,I.D. (2000) Substitution of Asp-210 in HAP1 (APE/Ref-1) eliminates endonuclease activity but stabilises substrate binding. Nucleic Acids Res., 28, 2207-2213.
22. Kunkel,T.A. (1985) Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc. Natl Acad. Sci. USA, 82, 488-492.
23. Slupphaug,G., Eftedal,I., Kavli,B., Bharati,S., Helle,N.M., Haug,T. Levine,D.W. and Krokan,H.E. (1995) Properties of a recombinant human uracil-DNA glycosylase from the UNG gene and evidence that UNG encodes the major uracil-DNA glycosylase. Biochemistry, 34, 128-138.
24. Krokan,H. and Wittwer,C.U. (1981) Uracil DNA-glycosylase from HeLa cells: General properties, substrate specificity and effect of uracil analogs. Nucleic Acids Res., 9, 2599-2613.
25. Pearl,L.H. (2000) Structure and function in the uracil-DNA glycosylase superfamily. Mutat. Res., 460, 165-181.
26. Sartori,A.A., Fitz-Gibbon,S., Yang,H., Miller,J.H. and Jiricny,J. (2002) A novel uracil-DNA glycosylase with broad substrate specificity and an unusual active site. EMBO J., 21, 3182-3191.
27. Elateri,I., Tinkelenberg,B.A., Hansbury,M., Caradonna,S., Muller-Weeks,S. and Ladner,R.D. (2003) hSMUG1 can functionally compensate for Ung1 in the yeast Saccharomyces cerevisiae. DNA Repair (Amst.), 2, 315-323.
28. Petersen-Mahrt,S.K., Harris,R.S. and Neuberger,M.S. (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature, 418, 99-103.
29. Otterlei,M., Kavli,B., Standal,R., Skjelbred,C., Bharati,S. and Krokan,H.E. (2000) Repair of chromosomal abasic sites in vivo involves at least three different repair pathways. EMBO J., 19, 5542-5551.
30. Lari,S.U., Chen,C.Y., Vertessy,B.G., Morre,J. and Bennett,S.E. (2006) Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance. DNA Repair (Amst.).
31. Mol,C.D., Arvai,A.S., Slupphaug,G., Kavli,B., Alseth,I., Krokan,H.E. and Tainer,J.A. (1995) Crystal structure and mutational analysis of human uracil-DNA glycosylase: Structural basis for specificity and catalysis. Cell, 80, 869-878.
32. Slupphaug,G., Mol,C.D., Kavli,B., Arvai,A.S., Krokan,H.E. and Tainer,J.A. (1996) A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature, 384, 87-92.
33. Kavli,B., Otterlei,M., Slupphaug,G. and Krokan,H.E. (2007) Uracil in DNA-general mutagen, but normal intermediate in acquired immunity. DNA Repair (Amst), 6, 505-516.
34. Parikh,S.S., Mol,C.D., Slupphaug,G., Bharati,S., Krokan,H.E. and Tainer,J.A. (1998) Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J., 17, 5214-5226.
35. Parikh,S.S., Walcher,G., Jones,G.D., Slupphaug,G., Krokan,H.E., Blackburn,G.M. and Tainer,J.A. (2000) Uracil-DNA glycosylase-DNA substrate and product structures: Conformational strain promotes catalytic efficiency by coupled stereoelectronic effects. Proc. Natl Acad. Sci. USA, 97, 5083-5088.
36. Bianchet,M.A., Seiple,L.A., Jiang,Y.L., Ichikawa,Y., Amzel,L.M. and Stivers,J.T. (2003) Electrostatic guidance of glycosyl cation migration along the reaction coordinate of uracil DNA glycosylase. Biochemistry 42, 12455-12460.
37. Krosky,D.J., Bianchet,M.A., Seiple,L., Chung,S., Amzel,L.M. and Stivers,J.T. (2006) Mimicking damaged DNA with a small molecule inhibitor of human UNG2. Nucleic Acids Res., 34, 5872-5879.
38. Dinner,A.R., Blackburn,G.M. and Karplus,M. (2001) Uracil-DNA glycosylase acts by substrate autocatalysis. Nature, 413, 752-755.
39. Ma,A., Hu,J., Karplus,M. and Dinner,A.R. (2006) Implications of alternative substrate binding modes for catalysis by uracil-DNA glycosylase: An apparent discrepancy resolved. Biochemistry, 45 13687-13696.
40. Drohat,A.C., Xiao,G., Tordova,M., Jagadeesh,J., Pankiewicz,K.W., Watanabe,K.A., Gilliland,G.L. and Stivers,J.T. (1999) Heteronuclear NMR and crystallographic studies of wild-type and H187Q Escherichia coli uracil DNA glycosylase: Electrophilic catalysis of uracil expulsion by a neutral histidine 187. Biochemistry, 38, 11876-11886.
41. Matsubara,M., TanakaT., Terato,H., Ohmae,E., lzumi,S., Katayanagi,K. and Ide,H. (2004) Mutational analysis of the damage-recognition and catalytic mechanism of human SMUG1 DNA glycosylase. Nucleic Acids Res., 32, 5291-5302.
42. Vidal,A.E., Hickson,I.D., Boiteux,S. and Radicella,J.P. (2001) Mechanism of stimulation of the DNA glycosylase activity of hOGG1 by the major liuman AP endonuclease: Bypass of the AP lyase activity step. Nucleic Acids Res., 29, 1285-1292.
43. Xia,L., Zheng,L., Lee,H.W., Bates,S.E., Federico,L., Shen,B. and O'Connor,T.R. (2005) Human 3-methyladenine-DNA glycosylase: Effect of sequence context on excision, association with PCNA, and stimulation by AP endonuclease. J. Mol. Biol., 346, 1259-1274.
44. Yang,H., Clendenin,W.M., Wong,D., Demple,B., Slupska,M.M., Chiang,J.H. and Miller,J.H. (2001) Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalin base excision repair of an A/GO mismatch. Nucleic Acids Res., 29, 743-752.
45. Akbari,M., Otterlei,M., Pena-Diaz,J., Aas,P.A., Kavli,B., Liabakk,N.B., Hagen,L., Imai,K., Durandy,A. et al. (2004) Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells. Nucleic Acids Res., 32, 5486-5498.
46. Eftedal,L., Guddal,P.H., Slupphaug,G., Volden,G. and Krokan,H.E. (1993) Consensus sequences for good and poor removal of uracil from double stranded DNA by uracil-DNA glycosylase. Nucleic Acids Res., 21 2095-2101.
47. Nilsen,H., Yazdankhah,S.P., Eftedal,I. and Krokan,H.E. (1995) Sequence specificity for removal of uracil from U.A pairs and U.G mismatches by uracil-DNA glycosylase from Escherichia coli, and correlation with mutational hotspots. FEBS Lett., 362, 205-209.
48. Bellamy,S.R. and Baldwin,G.S. (2001) A kinetic analysis of substrate recognition by uracil-DNA glycosylase from herpes simplex virus type 1. Nucleic Acids Res., 29, 3857-3863.
49. Ko,R. and Bennett,S.E. (2005) Physical and functional interaction of human nuclear uracil-DNA glycosylase with proliferating cell nuclear antigen. DNA Repair (Amst.), 4, 1421-1431.
50. Rada,C., Wiffiams,G.T., Nilsen,H., Barnes,D.E., Lindahl,T. and Neuberger,M.S. (2002) Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Curr. Biol. 12, 1748-1755.
51. Imai,K., Slupphaug,G., Lee,W.I., Revy,P., Nonoyama,S., Catalan,N., Yel,L., Forveille,M., Kavli,B. et al. (2003) Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat. Immunol., 4, 1023-1028.
52. Nilsen,H., Stamp,G., Andersen,S., Hrivnak,G., Krokan,H.E., Lindahl,T. and Barnes,D.E. (2003) Gene-targeted mice lacking the Ung uracil-DNA glycosylase develop B-cell lymphomas. Oncogene, 22, 5381-5386.
53. Andersen,S., Ericsson,M., Dai,H.Y., Pena-Diaz,J., Slupphaug,G., Nilsen,H., Aarset,H. and Krokan,H.E. (2005) Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice. DNA Repair (Amst.), 4, 1432-1441.
54. Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W. and Lipman,D.J. (1997) Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res., 25, 3389-3402.
55. Chenna,R., Sugawara,H., Koike,T., Lopez,R., Gibson,T.J., Higgins,D.G. and Thompson,J.D. (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res., 31, 3497-3500.
56. Clamp,M., Cuff,J., Searle,S.M. and Barton,G.J. (2004) The Jalview Java alignment editor. Bioinformatics, 20, 426-427.