Similarities and differences between "uncapped" telomeres and DNA double-strand breaks

Chromosoma

Volumn 121, Issue 2, 2012, Pages 117-130

  Dewar, James M ^a   Lydall, David ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DDC1 PROTEIN; DDC2 PROTEIN; DOUBLE STRANDED DNA; EXONUCLEASE; HELICASE; KU ANTIGEN; MEC1 PROTEIN; MEC3 PROTEIN; MRE11 PROTEIN; NUCLEIC ACID BINDING PROTEIN; PIF1 PROTEIN; PROTEIN RAD9; RAD17 PROTEIN; RAD50 PROTEIN; RAP1 PROTEIN; RIF1 PROTEIN; RIF2 PROTEIN; SGS1 PROTEIN; UNCLASSIFIED DRUG; XRS2 PROTEIN;

CELL CYCLE ARREST; DNA DAMAGE; DNA END JOINING REPAIR; DNA REPLICATION; DNA STRAND BREAKAGE; HUMAN; METAZOON; NONHUMAN; RECOMBINATION REPAIR; REVIEW; TELOMERE; YEAST;

ANIMALS; CELL CYCLE PROTEINS; CHROMOSOMAL PROTEINS, NON-HISTONE; DNA BREAKS, DOUBLE-STRANDED; DNA HELICASES; DNA REPAIR; EXODEOXYRIBONUCLEASES; MAMMALS; MODELS, BIOLOGICAL; MULTIPROTEIN COMPLEXES; SACCHAROMYCES CEREVISIAE PROTEINS; SACCHAROMYCETALES; TELOMERE; TELOMERE-BINDING PROTEINS;

EUKARYOTA; MAMMALIA; METAZOA; SACCHAROMYCETALES;

EID: 84859724110     PISSN: 00095915     EISSN: 14320886     Source Type: Journal    
DOI: 10.1007/s00412-011-0357-2     Document Type: Review

References (151)

1. Addinall SG, Holstein EM, Lawless C, Yu M, Chapman K, Banks AP, Ngo HP, Maringele L, Taschuk M, Young A, Ciesiolka A, Lister AL, Wipat A, Wilkinson DJ, Lydall D (2011) Quantitative fitness analysis shows that NMD proteins and many other protein complexes suppress or enhance distinct telomere cap defects. PLoS Genet 7(4):e1001362. doi:10.1371/journal.pgen.1001362
2. Agarwal R, Tang Z, Yu H, Cohen-Fix O (2003) Two distinct pathways for inhibiting pds1 ubiquitination in response to DNA damage. J Biol Chem 278(45):45027-45033. doi:10.1074/jbc.M306783200 (Pubitemid 37377263)
3. Allshire RC, Dempster M, Hastie ND (1989) Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic Acids Res 17(12):4611-4627 (Pubitemid 19165034)
4. Anbalagan S, Bonetti D, Lucchini G, Longhese MP (2011) Rif1 supports the function of the CST complex in yeast telomere capping. PLoS Genet 7(3):e1002024. doi:10.1371/journal.pgen.1002024
5. Aylon Y, Kupiec M (2003) The checkpoint protein Rad24 of Saccharomyces cerevisiae is involved in processing doublestrand break ends and in recombination partner choice. Mol Cell Biol 23(18):6585-6596 (Pubitemid 37075769)
6. Bae NS, Baumann P (2007) A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol Cell 26(3):323-334. doi:10.1016/j.molcel.2007.03.023 (Pubitemid 46687097)
7. Baumann P, Cech TR (2001) Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292(5519):1171-1175 (Pubitemid 32440940)
8. Bianchi A, de Lange T (1999) Ku binds telomeric DNA in vitro. J Biol Chem 274(30):21223-21227
9. Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E (1997) Telomeric localization of TRF2, a novel human telobox protein. Nat Genet 17(2):236-239. doi:10.1038/ng1097-236
10. Blankley RT, Lydall D (2004) A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J Cell Sci 117(Pt 4):601-608. doi:10.1242/jcs.00907 (Pubitemid 38240201)
11. Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91(1):25-34 (Pubitemid 27431310)
12. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279(5349):349-352 (Pubitemid 28063364)
13. Bombarde O, Boby C, Gomez D, Frit P, Giraud-Panis MJ, Gilson E, Salles B, Calsou P (2010) TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends. EMBO J 29 (9):1573-1584. doi:10.1038/emboj.2010.49
14. Bonetti D, Martina M, Clerici M, Lucchini G, Longhese MP (2009) Multiple pathways regulate 3′ overhang generation at S. cerevisiae telomeres. Mol Cell 35(1):70-81. doi:10.1016/j.molcel.2009.05.015
15. Bonetti D, Clerici M, Anbalagan S, Martina M, Lucchini G, Longhese MP (2010) Shelterin-like proteins and Yku inhibit nucleolytic processing of Saccharomyces cerevisiae telomeres. PLoS Genet 6(5):e1000966. doi:10.1371/journal.pgen.1000966
16. Broccoli D, Smogorzewska A, Chong L, de Lange T (1997) Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet 17(2):231-235. doi:10.1038/ng1097-231
17. Budd ME, Reis CC, Smith S, Myung K, Campbell JL (2006) Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta. Mol Cell Biol 26(7):2490-2500. doi:10.1128/MCB.26.7.2490-2500.2006
18. Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, Xu X, Deng CX, Finkel T, Nussenzweig M, Stark JM et al (2010) 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141(2):243-254. doi:10.1016/j.cell.2010.03.012
19. Cejka P, Cannavo E, Polaczek P, Masuda-Sasa T, Pokharel S, Campbell JL, Kowalczykowski SC (2010) DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2. Nature 467(7311):112-116. doi:10.1038/nature09355
20. Celli GB, de Lange T (2005) DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol 7(7):712-718. doi:10.1038/ncb1275 (Pubitemid 40975753)
21. Chang M, Luke B, Kraft C, Li Z, Peter M, Lingner J, Rothstein R (2009) Telomerase is essential to alleviate pif1-induced replication stress at telomeres. Genetics 183(3):779-791. doi:10.1534/genetics.109.107631
22. Chen SH, Smolka MB, Zhou H (2007) Mechanism of Dun1 activation by Rad53 phosphorylation in Saccharomyces cerevisiae. J Biol Chem 282(2):986-995. doi:10.1074/jbc.M609322200 (Pubitemid 47076565)
23. Cherry JM, Ball C, Weng S, Juvik G, Schmidt R, Adler C, Dunn B, Dwight S, Riles L, Mortimer RK, Botstein D (1997) Genetic and physical maps of Saccharomyces cerevisiae. Nature 387(6632 Suppl):67-73 (Pubitemid 27334668)
24. Chikashige Y, Hiraoka Y (2001) Telomere binding of the Rap1 protein is required for meiosis in fission yeast. Curr Biol 11(20):1618-1623 (Pubitemid 32978529)
25. Chung WH, Zhu Z, Papusha A, Malkova A, Ira G (2010) Defective resection at DNA double-strand breaks leads to de novo telomere formation and enhances gene targeting. PLoS Genet 6(5): e1000948. doi:10.1371/journal.pgen.1000948
26. Churikov D, Price CM (2008) Pot1 and cell cycle progression cooperate in telomere length regulation. Nat Struct Mol Biol 15(1):79-84. doi:10.1038/nsmb1331
27. Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179-204. doi:10.1016/ j.molcel.2010.09.019
28. Cimino-Reale G, Pascale E, Alvino E, Starace G, D'Ambrosio E (2003) Long telomeric C-rich 5′-tails in human replicating cells. J Biol Chem 278(4):2136-2140 (Pubitemid 36801278)
29. Ciosk R, Zachariae W, Michaelis C, Shevchenko A, Mann M, Nasmyth K (1998) An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell 93(6):1067-1076 (Pubitemid 28280799)
30. Cooper JP, Nimmo ER, Allshire RC, Cech TR (1997) Regulation of telomere length and function by a Myb-domain protein in fission yeast. Nature 385(6618):744-747. doi:10.1038/385744a0 (Pubitemid 27098098)
31. Cooper JP, Watanabe Y, Nurse P (1998) Fission yeast Taz1 protein is required for meiotic telomere clustering and recombination. Nature 392(6678):828-831. doi:10.1038/33947 (Pubitemid 28225325)
32. Cotta-Ramusino C, McDonald ER 3rd, Hurov K, Sowa ME, Harper JW, Elledge SJ (2011) A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science 332(6035):1313-1317. doi:10.1126/science.1203430
33. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426(6963):194-198. doi:10.1038/nature02118 (Pubitemid 37442589)
34. de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19(18):2100-2110. doi:10.1101/gad.1346005
35. de Lange T (2009) How telomeres solve the end-protection problem. Science 326(5955):948-952. doi:10.1126/science.1170633
36. de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM, Varmus HE (1990) Structure and variability of human chromosome ends. Mol Cell Biol 10(2):518-527
37. Dewar JM, Lydall D (2010) Pif1- and Exo1-dependent nucleases coordinate checkpoint activation following telomere uncapping. EMBO J 29(23):4020-4034. doi:10.1038/emboj.2010.267
38. Downs JA, Allard S, Jobin-Robitaille O, Javaheri A, Auger A, Bouchard N, Kron SJ, Jackson SP, Cote J (2004) Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol Cell 16(6):979-990. doi:10.1016/j.molcel.2004.12.003 (Pubitemid 40018407)
39. Ellison V, Stillman B (2003) Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5′ recessed DNA. PLoS Biol 1(2): E33. doi:10.1371/journal.pbio.0000033
40. Falck J, Coates J, Jackson SP (2005) Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434(7033):605-611 (Pubitemid 40488547)
41. Faure V, Coulon S, Hardy J, Geli V (2010) Cdc13 and telomerase bind through different mechanisms at the lagging- and leading-strand telomeres. Mol Cell 38(6):842-852. doi:10.1016/j.molcel.2010.05.016
42. Feldmann H, Winnacker EL (1993) A putative homologue of the human autoantigen Ku from Saccharomyces cerevisiae. J Biol Chem 268(17):12895-12900 (Pubitemid 23182461)
43. Foster SS, Zubko MK, Guillard S, Lydall D (2006) MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants. DNA Repair (Amst) 5(7):840-851 (Pubitemid 43928887)
44. Foster SS, Balestrini A, Petrini JH (2011) Functional interplay of the Mre11 nuclease and Ku in the response to replication-associated DNA damage. Mol Cell Biol. doi:10.1128/MCB.05854-11
45. Frank-Vaillant M, Marcand S (2002) Transient stability of DNA ends allows nonhomologous end joining to precede homologous recombination. Molecular cell 10(5):1189-1199 (Pubitemid 35453835)
46. Fuster JJ, Andres V (2006) Telomere biology and cardiovascular disease. Circ Res 99(11):1167-1180. doi:10.1161/01. RES.0000251281.00845.18
47. Gao H, Cervantes RB, Mandell EK, Otero JH, Lundblad V (2007) RPA-like proteins mediate yeast telomere function. Nat Struct Mol Biol 14(3):208-214 (Pubitemid 46355575)
48. Gardner R, Putnam CW, Weinert T (1999) RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. EMBO J 18(11):3173-3185. doi:10.1093/emboj/18.11.3173 (Pubitemid 29255625)
49. Garvik B, Carson M, Hartwell L (1995) Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol Cell Biol 15(11):6128-6138
50. Gravel S, Larrivee M, Labrecque P, Wellinger RJ (1998) Yeast Ku as a regulator of chromosomal DNA end structure. Science 280 (5364):741-744 (Pubitemid 28243349)
51. Gravel S, Chapman JR, Magill C, Jackson SP (2008) DNA helicases Sgs1 and BLM promote DNA double-strand break resection. Genes Dev 22(20):2767-2772. doi:10.1101/gad.503108
52. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999) Mammalian telomeres end in a large duplex loop. Cell 97(4):503-514 (Pubitemid 29231173)
53. Haber JE (2002) Uses and abuses of HO endonuclease. Methods Enzymol 350:141-164
54. Hammet A, Magill C, Heierhorst J, Jackson SP (2007) Rad9 BRCT domain interaction with phosphorylated H2AX regulates the G1 checkpoint in budding yeast. EMBO Rep 8(9):851-857. doi:10.1038/sj.embor.7401036 (Pubitemid 350001429)
55. Harrison JC, Haber JE (2006) Surviving the breakup: the DNA damage checkpoint. Annu Rev Genet 40:209-235. doi:10.1146/annurev. genet.40.051206. 105231
56. Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, Dokal I (1998) X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 19(1):32-38. doi:10.1038/ng0598-32 (Pubitemid 28242019)
57. Hockemeyer D, Palm W, Else T, Daniels JP, Takai KK, Ye JZ, Keegan CE, de Lange T, Hammer GD (2007) Telomere protection by mammalian Pot1 requires interaction with Tpp 1. Nat Struct Mol Biol 14(8):754-761. doi:10.1038/nsmb1270 (Pubitemid 47220056)
58. Houghtaling BR, Cuttonaro L, Chang W, Smith S (2004) A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr Biol 14(18):1621-1631. doi:10.1016/j.cub.2004.08.052 (Pubitemid 39239358)
59. Hsu HL, Gilley D, Blackburn EH, Chen DJ (1999) Ku is associated with the telomere in mammals. Proc Natl Acad Sci U S A 96 (22):12454-12458 (Pubitemid 29513523)
60. Hsu HL, Gilley D, Galande SA, Hande MP, Allen B, Kim SH, Li GC, Campisi J, Kohwi-Shigematsu T, Chen DJ (2000) Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev 14(22):2807-2812
61. Hu F, Wang Y, Liu D, Li Y, Qin J, Elledge SJ (2001) Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell 107(5):655-665 (Pubitemid 34014866)
62. Ivanov EL, Sugawara N, White CI, Fabre F, Haber JE (1994) Mutations in XRS2 and RAD50 delay but do not prevent mating-type switching in Saccharomyces cerevisiae. Mol Cell Biol 14(5):3414-3425 (Pubitemid 24132752)
63. Jain D, Cooper JP (2010) Telomeric strategies: means to an end. Annu Rev Genet 44:243-269. doi:10.1146/annurev-genet-102108-134841
64. Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, Jackson SP (2006) ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8(1):37-45. doi:10.1038/ncb1337 (Pubitemid 43064795)
65. Jia X, Weinert T, Lydall D (2004) Mec1 and Rad53 inhibit formation of single-stranded DNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 166(2):753-764 (Pubitemid 38391740)
66. Kanoh J, Ishikawa F (2001) spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast. Curr Biol 11(20):1624-1630 (Pubitemid 32978530)
67. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T (1999) p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283(5406):1321-1325
68. Kelleher C, Kurth I, Lingner J (2005) Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro. Mol Cell Biol 25(2):808-818 (Pubitemid 40096600)
69. Kim EM, Burke DJ (2008) DNA damage activates the SAC in an ATM/ATR-dependent manner, independently of the kinetochore. PLoS Genet 4(2):e1000015. doi:10.1371/journal.pgen.1000015
70. Kim SH, Kaminker P, Campisi J (1999) TIN2, a new regulator of telomere length in human cells. Nat Genet 23(4):405-412. doi:10.1038/70508
71. Lahaye A, Stahl H, Thines-Sempoux D, Foury F (1991) PIF1: a DNA helicase in yeast mitochondria. EMBO J 10(4):997-1007 (Pubitemid 21905559)
72. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860-921. doi:10.1038/35057062
73. Lansdorp PM (2009) Telomeres and disease. EMBO J 28(17):2532-2540. doi:10.1038/emboj.2009.172
74. Lazzaro F, Sapountzi V, Granata M, Pellicioli A, Vaze M, Haber JE, Plevani P, Lydall D, Muzi-Falconi M (2008) Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. EMBO J 27(10):1502-1512. doi:10.1038/emboj.2008.81 (Pubitemid 351733336)
75. Lee HW, Blasco MA, Gottlieb GJ, Horner JW 2nd, Greider CW, DePinho RA (1998a) Essential role of mouse telomerase in highly proliferative organs. Nature 392(6676):569-574. doi:10.1038/33345 (Pubitemid 28207706)
76. Lee SE, Moore JK, Holmes A, Umezu K, Kolodner RD, Haber JE (1998b) Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Cell 94 (3):399-409 (Pubitemid 28376083)
77. Lee SJ, Schwartz MF, Duong JK, Stern DF (2003) Rad53 phosphorylation site clusters are important for Rad53 regulation and signaling. Mol Cell Biol 23(17):6300-6314 (Pubitemid 37013106)
78. Li B, Oestreich S, de Lange T (2000) Identification of human Rap1: implications for telomere evolution. Cell 101(5):471-483
79. Lin TT, Letsolo BT, Jones RE, Rowson J, Pratt G, Hewamana S, Fegan C, Pepper C, Baird DM (2010) Telomere dysfunction and fusion during the progression of chronic lymphocytic leukemia: evidence for a telomere crisis. Blood 116(11):1899-1907. doi:10.1182/blood-2010-02-272104
80. Lisby M, Barlow JH, Burgess RC, Rothstein R (2004) Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 118(6):699-713. doi:10.1016/j.cell.2004.08.015 (Pubitemid 39221730)
81. Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (2004) PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol 6(7):673-680. doi:10.1038/ncb1142 (Pubitemid 38960926)
82. Loayza D, De Lange T (2003) POT1 as a terminal transducer of TRF1 telomere length control. Nature 423(6943):1013-1018 (Pubitemid 36806919)
83. Lopes J, Piazza A, Bermejo R, Kriegsman B, Colosio A, Teulade- Fichou MP, Foiani M, Nicolas A (2011) G-quadruplex-induced instability during leading-strand replication. EMBO J. doi:10.1038/emboj.2011.316
84. Lydall D (2009) Taming the tiger by the tail: modulation of DNA damage responses by telomeres. EMBO J 28(15):2174-2187. doi:10.1038/emboj.2009.176
85. Lydall D, Weinert T (1995) Yeast checkpoint genes in DNA damage processing: implications for repair and arrest. Science 270 (5241):1488-1491
86. Majka J, Burgers PM (2003) Yeast Rad17/Mec3/Ddc1: a sliding clamp for the DNA damage checkpoint. Proc Natl Acad Sci U S A 100 (5):2249-2254 (Pubitemid 36297485)
87. Mandell EK, Gelinas AD, Wuttke DS, Lundblad V (2011) Sequencespecific binding to telomeric DNA is not a conserved property of the Cdc13 DNA binding domain. Biochemistry 50(29):6289-6291. doi:10.1021/bi2005448
88. Mantiero D, Clerici M, Lucchini G, Longhese MP (2007) Dual role for Saccharomyces cerevisiae Tel1 in the checkpoint response to double-strand breaks. EMBO Rep 8(4):380-387 (Pubitemid 46511039)
89. Marcand S, Pardo B, Gratias A, Cahun S, Callebaut I (2008) Multiple pathways inhibit NHEJ at telomeres. Genes Dev 22(9):1153-1158. doi:10.1101/gad.455108 (Pubitemid 351656575)
90. Maringele L, Lydall D (2002) EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes Dev 16(15):1919-1933 (Pubitemid 34832921)
91. Mimitou EP, Symington LS (2008) Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature 455(7214):770-774. doi:10.1038/ nature07312
92. Mimitou EP, Symington LS (2009) DNA end resection: many nucleases make light work. DNA Repair (Amst) 8(9):983-995. doi:10.1016/j.dnarep.2009.04.017
93. Mimitou EP, Symington LS (2010) Ku prevents Exo1 and Sgs1- dependent resection of DNA ends in the absence of a functional MRX complex or Sae2. EMBO J 29(19):3358-3369. doi:10.1038/emboj.2010.193
94. Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T, Nojima A, Nabetani A, Oike Y, Matsubara H, Ishikawa F, Komuro I (2009) A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med 15(9):1082-1087. doi:10.1038/nm.2014
95. Mitchell JR, Wood E, Collins K (1999) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402 (6761):551-555. doi:10.1038/990141
96. Miyake Y, Nakamura M, Nabetani A, Shimamura S, Tamura M, Yonehara S, Saito M, Ishikawa F (2009) RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol Cell 36 (2):193-206. doi:10.1016/j.molcel.2009.08.009
97. Miyoshi T, Kanoh J, Saito M, Ishikawa F (2008) Fission yeast Pot1-Tpp 1 protects telomeres and regulates telomere length. Science 320(5881):1341-1344. doi:10.1126/science.1154819 (Pubitemid 351929470)
98. Nakada D, Matsumoto K, Sugimoto K (2003) ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism. Genes Dev 17(16):1957-1962 (Pubitemid 36999322)
99. Navadgi-Patil VM, Burgers PM (2009) A tale of two tails: activation of DNA damage checkpoint kinase Mec1/ATR by the 9-1-1 clamp and by Dpb11/TopBP1. DNA Repair (Amst) 8(9):996-1003. doi:10.1016/j.dnarep.2009.03.011
100. Ngo HP, Lydall D (2010) Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS Genet 6(8):e1001072. doi:10.1371/journal.pgen.1001072
101. Nicolette ML, Lee K, Guo Z, Rani M, Chow JM, Lee SE, Paull TT (2010) Mre11-Rad50-Xrs2 and Sae2 promote 5′ strand resection of DNA double-strand breaks. Nat Struct Mol Biol 17(12):1478-1485. doi:10.1038/nsmb.1957
102. Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC (2011) BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev 25(4):350-362. doi:10.1101/gad.2003811
103. Niu H, Chung WH, Zhu Z, Kwon Y, Zhao W, Chi P, Prakash R, Seong C, Liu D, Lu L, Ira G, Sung P (2010) Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature 467(7311):108-111. doi:10.1038/nature09318
104. Oganesian L, Karlseder J (2011) Mammalian 5′ C-rich telomeric overhangs are a mark of recombination-dependent telomere maintenance. Molecular cell 42(2):224-236. doi:10.1016/j.molcel.2011.03.015
105. Ohki R, Ishikawa F (2004) Telomere-bound TRF1 and TRF2 stall the replication fork at telomeric repeats. Nucleic Acids Res 32 (5):1627-1637. doi:10.1093/nar/gkh309 (Pubitemid 38832708)
106. Olovnikov AM (1971) Principle of marginotomy in template synthesis of polynucleotides. Dokl Akad Nauk SSSR 201(6):1496-1499
107. Paeschke K, Capra JA, Zakian VA (2011) DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase. Cell 145(5):678-691. doi:10.1016/j.cell.2011.04.015
108. Palm W, Hockemeyer D, Kibe T, de Lange T (2009) Functional dissection of human and mouse POT1 proteins. Mol Cell Biol 29(2):471-482. doi:10.1128/MCB. 01352-08
109. Pardo B, Marcand S (2005) Rap1 prevents telomere fusions by nonhomologous end joining. EMBO J 24(17):3117-3127. doi:10.1038/sj.emboj.7600778 (Pubitemid 41486347)
110. Pfander B, Diffley JF (2011) Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. EMBO J. doi:10.1038/emboj.2011.345
111. Pike JE, Burgers PM, Campbell JL, Bambara RA (2009) Pif1 helicase lengthens some Okazaki fragment flaps necessitating Dna2 nuclease/ helicase action in the two-nuclease processing pathway. J Biol Chem 284(37):25170-25180. doi:10.1074/jbc.M109.023325
112. Pitt CW, Cooper JP (2010) Pot1 inactivation leads to rampant telomere resection and loss in one cell cycle. Nucleic Acids Res. doi:10.1093/nar/gkq580
113. Polotnianka RM, Li J, Lustig AJ (1998) The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities. Curr Biol 8(14):831-834 (Pubitemid 28324538)
114. Ribeyre C, Lopes J, Boule JB, Piazza A, Guedin A, Zakian VA, Mergny JL, Nicolas A (2009) The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo. PLoS Genet 5(5):e1000475. doi:10.1371/journal.pgen.1000475
115. Samper E, Goytisolo FA, Slijepcevic P, van Buul PP, Blasco MA (2000) Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO Rep 1(3):244-252. doi:10.1093/embo-reports/kvd051
116. Sanchez Y, Bachant J, Wang H, Hu F, Liu D, Tetzlaff M, Elledge SJ (1999) Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science 286 (5442):1166-1171
117. Sandell LL, Zakian VA (1993) Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 75(4):729-739 (Pubitemid 23346371)
118. Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP (2007) Human CtIP promotes DNA end resection. Nature 450(7169):509-514. doi:10.1038/nature06337 (Pubitemid 350190253)
119. Segurado M, Diffley JF (2008) Separate roles for the DNA damage checkpoint protein kinases in stabilizing DNA replication forks. Genes Dev 22(13):1816-1827. doi:10.1101/gad.477208 (Pubitemid 351915506)
120. Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, de Lange T (2009) Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138(1):90-103. doi:10.1016/j.cell.2009.06.021
121. Sfeir A, Kabir S, van Overbeek M, Celli GB, de Lange T (2010) Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. Science 327(5973):1657-1661. doi:10.1126/science.1185100
122. Shampay J, Blackburn EH (1988) Generation of telomere-length heterogeneity in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 85(2):534-538
123. Shore D, Nasmyth K (1987) Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements. Cell 51(5):721-732
124. Stansel RM, de Lange T, Griffith JD (2001) T-loop assembly in vitro involves binding of TRF2 near the 3′ telomeric overhang. EMBO J 20(19):5532-5540. doi:10.1093/emboj/20.19.5532 (Pubitemid 32959473)
125. Sun Z, Hsiao J, Fay DS, Stern DF (1998) Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Science 281(5374):272-274 (Pubitemid 28334513)
126. Surovtseva YV, Churikov D, Boltz KA, Song X, Lamb JC, Warrington R, Leehy K, Heacock M, Price CM, Shippen DE (2009) Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Mol Cell 36(2):207-218. doi:10.1016/j.molcel.2009.09.017
127. Takai H, Smogorzewska A, de Lange T (2003) DNA damage foci at dysfunctional telomeres. Curr Biol 13(17):1549-1556 (Pubitemid 37078413)
128. Teo SH, Jackson SP (2001) Telomerase subunit overexpression suppresses telomere-specific checkpoint activation in the yeast yku80 mutant. EMBO Rep 2(3):197-202. doi:10.1093/embo-reports/kve038
129. Torres JZ, Schnakenberg SL, Zakian VA (2004) Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities. Mol Cell Biol 24(8):3198-3212 (Pubitemid 38452066)
130. Tsubouchi H, Ogawa H (2000) Exo1 roles for repair of DNA doublestrand breaks and meiotic crossing over in Saccharomyces cerevisiae. Mol Biol Cell 11(7):2221-2233 (Pubitemid 30489910)
131. Usui T, Ogawa H, Petrini JH (2001) A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol Cell 7(6):1255-1266 (Pubitemid 32607359)
132. Usui T, Foster SS, Petrini JH (2009) Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization. Mol Cell 33(2):147-159. doi:10.1016/j.molcel.2008.12.022
133. van Steensel B, de Lange T (1997) Control of telomere length by the human telomeric protein TRF1. Nature 385(6618):740-743
134. Vega LR, Phillips JA, Thornton BR, Benanti JA, Onigbanjo MT, Toczyski DP, Zakian VA (2007) Sensitivity of yeast strains with long G-tails to levels of telomere-bound telomerase. PLoS Genet 3(6):e105. doi:10.1371/journal.pgen. 0030105
135. Venclovas C, Thelen MP (2000) Structure-based predictions of Rad1, Rad9, Hus1 and Rad17 participation in sliding clamp and clamp-loading complexes. Nucleic Acids Res 28(13):2481-2493 (Pubitemid 30420845)
136. Vodenicharov MD, Wellinger RJ (2006) DNA degradation at unprotected telomeres in yeast is regulated by the CDK1 (Cdc28/Clb) cell-cycle kinase. Mol Cell 24(1):127-137 (Pubitemid 44466679)
137. Vodenicharov MD, Laterreur N, Wellinger RJ (2010) Telomere capping in non-dividing yeast cells requires Yku and Rap1. EMBO J: In Press. doi:10.1038/emboj.2010.155
138. Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413 (6854):432-435. doi:10.1038/35096585 (Pubitemid 32928599)
139. Wang Y, Ghosh G, Hendrickson EA (2009) Ku86 represses lethal telomere deletion events in human somatic cells. Proc Natl Acad Sci U S A 106(30):12430-12435. doi:10.1073/pnas.0903362106
140. Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239 (94):197-201
141. Wotton D, Shore D (1997) A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev 11(6):748-760 (Pubitemid 27157163)
142. Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, Bachilo O, Pathak S, Tahara H, Bailey SM, Behringer RR, Chang S (2006) Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 126(1):49-62. doi:10.1016/j.cell.2006.05.037
143. Wysocki R, Javaheri A, Allard S, Sha F, Cote J, Kron SJ (2005) Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol 25(19):8430-8443. doi:10.1128/MCB.25.19.8430- 8443.2005
144. Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (2004) POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/ TRF1 complex. Genes Dev 18(14):1649-1654. doi:10.1101/gad.1215404 (Pubitemid 38938182)
145. Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Leger A, Poulet A, Benarroch D, Magdinier F, Morere J, Amiard S, Verhoeyen E, Britton S, Calsou P, Salles B, Bizard A et al (2010) TRF2 and Apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell 142(2):230-242. doi:10.1016/j.cell.2010.05.032
146. Zhao X, Rothstein R (2002) The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1. Proc Natl Acad Sci U S A 99(6):3746-3751. doi:10.1073/pnas.062502299 (Pubitemid 34252177)
147. Zhong Z, Shiue L, Kaplan S, de Lange T (1992) A mammalian factor that binds telomeric TTAGGG repeats in vitro. Mol Cell Biol 12 (11):4834-4843
148. Zhou J, Monson EK, Teng SC, Schulz VP, Zakian VA (2000) Pif1p helicase, a catalytic inhibitor of telomerase in yeast. Science 289 (5480):771-774 (Pubitemid 30650196)
149. Zhu Z, Chung WH, Shim EY, Lee SE, Ira G (2008) Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 134(6):981-994. doi:10.1016/j.cell.2008.08.037
150. Zou L, Elledge SJ (2003) Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300(5625):1542-1548. doi:10.1126/science.1083430 (Pubitemid 36682880)
151. Zubko MK, Guillard S, Lydall D (2004) Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 168(1):103-115 (Pubitemid 39346582)