Repeat instability during DNA repair: Insights from model systems

Critical Reviews in Biochemistry and Molecular Biology

Volumn 50, Issue 2, 2015, Pages 142-167

  Usdin, Karen ^a   House, Nealia C M ^b   Freudenreich, Catherine H ^b  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b TUFTS UNIVERSITY   (United States)

Author keywords

Chromosome fragility; DNA damage checkpoint; DNA structure; Recombination; Repair; Replication; Structure specific helicases; Trinucleotide repeat expansion

Indexed keywords

CIS ACTING ELEMENT; DOUBLE STRANDED DNA; HELICASE; MISMATCH REPAIR PROTEIN; REPETITIVE DNA; TRANS ACTING FACTOR; DNA;

CHROMOSOME FRAGILITY; DNA DAMAGE; DNA DAMAGE CHECKPOINT; DNA END JOINING REPAIR; DNA REPAIR; DNA REPLICATION; DNA STRAND BREAKAGE; DNA STRUCTURE; EXCISION REPAIR; GENETIC DISORDER; GENOMIC INSTABILITY; HOMOLOGOUS RECOMBINATION; HUMAN; MISMATCH REPAIR; NONHUMAN; PRIORITY JOURNAL; RECOMBINATION REPAIR; REVIEW; SINGLE STRAND ANNEALING; TRINUCLEOTIDE REPEAT; CHEMISTRY; CLASSIFICATION; CONFORMATION; GENETIC DISEASES, INBORN; GENETIC RECOMBINATION; GENETICS;

CHROMOSOME FRAGILITY; DNA; DNA DAMAGE; DNA REPAIR; DNA REPLICATION; GENETIC DISEASES, INBORN; GENOMIC INSTABILITY; HUMANS; NUCLEIC ACID CONFORMATION; RECOMBINATION, GENETIC; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 84928791696     PISSN: 10409238     EISSN: 15497798     Source Type: Journal    
DOI: 10.3109/10409238.2014.999192     Document Type: Review

References (306)

1. Anand RP, Shah KA, Niu H, et al. (2012). Overcoming natural replication barriers: differential helicase requirements. Nucleic Acids Res 40: 1091-105
2. Balakumaran BS, Freudenreich CH, Zakian VA. (2000). CGG/CCG repeats exhibit orientation-dependent instability anDorientationindependent fragilitYin Saccharomyces cerevisiae. Hum Mol Genet 9: 93-100
3. Belotserkovskii BP, Liu R, Tornaletti S, et al. (2010). Mechanisms and implications of transcription blockage by guanine-rich DNA sequences. Proc Natl Acad Sci USA 107: 12816-21
4. Belotserkovskii BP, Mirkin SM, Hanawalt PC. (2013). DNA sequences that interfere with transcription: implications for genome function and stability. Chem Rev 113: 8620-37
5. Bergoglio V, Boyer AS, Walsh E, et al. (2013). DNA synthesis by Pol eta promotes fragile site stability by preventing under-replicated DNA in mitosis. J Cell Biol 201: 395-408
6. Bhattacharyya S, Lahue RS. (2004). Saccharomyces cerevisiae Srs2 DNA helicase selectively blocks expansions of trinucleotide repeats. Mol Cell Biol 24: 7324-30
7. Bhattacharyya S, Lahue RS. (2005). Srs2 helicase of Saccharomyces cerevisiae selectively unwinds triplet repeat DNA. J Biol Chem 280: 33311-17
8. Biffi G, Tannahill D, McCafferty J, Balasubramanian S. (2013). Quantitative visualization of DNA G-quadruplex structures in human cells. Nat Chem 5: 182-6
9. Boiteux S, Jinks-Robertson S. (2013). DNA repair mechanisms and the bypass of DNA damage in Saccharomyces cerevisiae. Genetics 193: 1025-64
10. Bourn RL, De Biase I, Pinto RM, et al. (2012). Pms2 suppresses large expansions of the (GAA.TTC)n sequence in neuronal tissues. PLoS One 7: e47085
11. Bowater RP, Jaworski A, Larsonje, et al. (1997). Transcription increases the deletion frequency of long CTG.CAG triplet repeats from plasmids in Escherichia coli. Nucleic Acids Res 25: 2861-8
12. Brock GJ, Anderson NH, Monckton DG. (1999). Cis-Acting modifiers of expanded CAG/CTG triplet repeatexpandability: associations with flanking GC content and proximity to CpG islands. Hum Mol Genet 8: 1061-7
13. Byun TS, Pacek M, Yee MC, et al. (2005). Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATRdependent checkpoint. Genes Dev 19: 1040-52
14. Callahan JL, Andrews KJ, Zakian VA, Freudenreich CH. (2003). Mutations in yeast replication proteins that increase CAG/CTG expansions also increase repeat fragility. Mol Cell Biol 23: 7849-60
15. Cannavo E, Marra G, Sabates-Bellver J, et al. (2005). Expression of the MutL homologue hMLH3 in human cells and its role in DNA mismatch repair. Cancer Res 65: 10759-66
16. Casella M, Lucarelli M, Simili M, et al. (2003). Spontaneous chromosome loss and colcemid resistance in lymphocytes from patients with myotonic dystrophy type 1. Cytogenet Genome Res 100: 224-9
17. Chan NL, Guo J, Zhang T, et al. (2013). Coordinated processing of 30 slipped (CAG)n/(CTG)n hairpins by DNA polymerases beta and delta preferentiallYinduces repeatexpansions. J Biol Chem 288: 15015-22
18. Chan NL, Hou C, Zhang T, et al. (2012). The Werner syndrome protein promotes CAG/CTG repeat stability by resolving large (CAG)(n)/.(CTG)(n) hairpins. J Biol Chem 287: 30151-6
19. Chan SH, Yu AM, McVey M. (2010). Dual roles for DNA polymerase theta in alternative end-joining repair of double-strand breaks in Drosophila. PLoS Genet 6: e1001005
20. Chapman JR, Taylor MR, Boulton SJ. (2012). Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47: 497-510
21. Charbonneau N, Amunugama R, Schmutte C, et al. (2009). Evidence thaThMLH3 functions primarilYin meiosis and in hMSH2-hMSH3 mismatch repair. Cancer Biol Ther 8: 1411-20
22. Cherng N, Shishkin AA, Schlager LI, et al. (2011). Expansions, contractions, and fragility of the spinocerebellar ataxia type 10 pentanucleotide repeat in yeast. Proc Natl Acad Sci USA 108: 2843-8
23. Chung MY, Ranum LP, Duvick LA, et al. (1993). Evidence for a mechanism predisposing to intergenerational CAG repeat instabilitYin spinocerebellar ataxia type I. Nat Genet 5: 254-8
24. Claassen DA, Lahue RS. (2007). Expansions of CAG.CTG repeats in immortalized human astrocytes. Hum Mol Genet 16: 3088-96
25. Clark RM, De Biase I, Malykhina AP, et al. (2007). The GAA tripletrepeat is unstable in the context of the human FXN locus and displays age-dependentexpansions in cerebellum and DRG in a transgenic mouse model. Hum Genet 120: 633-40
26. Cleary JD, Nichol K, Wang YH, Pearson CE. (2002). Evidence of cisacting factors in replication-mediated trinucleotide repeat instabilitYin primate cells. Nat Genet 31: 37-46
27. Cleary JD, Pearson CE. (2005). Replication fork dynamics and dynamic mutations: the fork-shift model of repeat instability. Trends Genet 21: 272-80
28. Cleary JD, Tome S, Lopez Castel A, et al. (2010). Tissue- And agespecific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus. Nat Struct Mol Biol 17: 1079-87
29. Crespan E, Czabany T, Maga G, Hubscher U. (2012). Microhomologymediated DNA strand annealing and elongation by human DNA polymerases lambda and beta on normal and repetitive DNA sequences. Nucleic Acids Res 40: 5577-90
30. Daee DL, Mertz T, Lahue RS. (2007). Postreplication repair inhibits CAG.CTG repeatexpansions in Saccharomyces cerevisiae. Mol Cell Biol 27: 102-10
31. De Temmerman N, Sermon K, Seneca S, et al. (2004). Intergenerational instability of the expanded CTG repeat in the DMPK gene: studies in human gametes and preimplantation embryos. Am J Hum Genet 75: 325-9
32. Dean NL, Tan SL, Ao A. (2006). InstabilitYin the transmission of the myotonic dystrophy CTG repeat in human oocytes and preimplantation embryos. Fertil Steril 86: 98-105
33. Debacker K, Frizzell A, Gleeson O, et al. (2012). Histone deacetylase complexes promote trinucleotide repeatexpansions. PLoS Biol 10: e1001257
34. Deem A, Keszthelyi A, Blackgrove T, et al. (2011). Break-induced replication is highlYinaccurate. PLoS Biol 9: e1000594
35. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, et al. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72: 245-56
36. Dhar A, Lahue RS. (2008). Rapid unwinding of triplet repeaThairpins by Srs2 helicase of Saccharomyces cerevisiae. Nucleic Acids Res 36: 3366-73
37. Dion V. (2014). Tissue specificitYin DNA repair: lessons from trinucleotide repeat instability. Trends Genet: TIG 30: 220-9
38. Dion V, Lin Y, Hubert Jr L, et al. (2008). Dnmt1 deficiency promotes CAG repeatexpansion in the mouse germline. Hum Mol Genet 17: 1306-17
39. Dion V, Wilson JH. (2009). Instability and chromatin structure of expanded trinucleotide repeats. Trends Genet: TIG 25: 288-97
40. Dixon MJ, Lahue R. (2002). Examining the potential role of DNA polymerases eta and zeta in triplet repeat instabilitYin yeast. DNA Repair 1: 763-70
41. Dragileva E, Hendricks A, Teed A, et al. (2009). Intergenerational and striatal CAG repeat instabilitYin Huntington's disease knock-in mice involve different DNA repair genes. Neurobiol Dis 33: 37-47
42. Du J, Campau E, Soragni E, et al. (2013). Length-dependent CTG.CAG triplet-repeatexpansion in myotonic dystrophy patient-derived induced pluripotent stem cells. Hum Mol Genet 22: 5276-87
43. Du J, Campau E, Soragni E, et al. (2012). Role of mismatch repair enzymes in GAA.TTC triplet-repeatexpansion in Friedreich ataxia induced pluripotent stem cells. J Biol Chem 287: 29861-72
44. Duquette ML, Handa P, Vincent JA, et al. (2004). Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes Dev 18: 1618-29
45. Dure St L, Landwehrmeyer GB, Golden J, et al. (1994). IT15 gene expression in fetal human brain. Brain Res 659: 33-41
46. eichler EE, Holden JJ, Popovich BW, et al. (1994). Length of uninterrupted CGG repeats determines instabilitYin the FMR1 gene. Nat Genet 8: 88-94
47. ennis S, Murray A, Brightwell G, et al. (2007). Closely linked cis-Acting modifier of expansion of the CGG repeat in high risk FMR1 haplotypes. Hum Mutat 28: 1216-24
48. entezam A, Lokanga AR, Le W, et al. (2010). Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeatexpansion in a fragile X premutation mouse model. Hum Mutat 31: 611-16
49. entezam A, Usdin K. (2008). ATR protects the genome against CGG.CCG-repeatexpansion in Fragile X premutation mice. Nucleic Acids Res 36: 1050-6
50. entezam A, Usdin K. (2009). ATM and ATR protect the genome against two different types of tandem repeat instabilitYin Fragile X premutation mice. Nucleic Acids Res 37: 6371-7
51. erlich RL, Fry RC, Begley TJ, et al. (2008). Anc1, a protein associated with multiple transcription complexes, is involved in postreplication repair pathwaYin S. cerevisiae. PLoS One 3: e3717
52. errico A, Costanzo V. (2012). Mechanisms of replication fork protection: a safeguard for genome stability. Crit Rev Biochem Mol Biol 47: 222-35
53. ezzatizadeh V, Pinto RM, Sandi C, et al. (2012). The mismatch repair system protects against intergenerational GAA repeat instabilitYin a Friedreich ataxia mouse model. Neurobiol Dis 46: 165-71
54. ezzatizadeh V, Sandi C, Sandi M, et al. (2014). MutLalpha heterodimers modify the molecular phenotype of Friedreich ataxia. PLoS One 9: e100523
55. Foiry L, Dong L, Savouret C, et al. (2006). Msh3 is Alimiting factor in the formation of intergenerational CTG expansions in DM1 transgenic mice. Human Genet 119: 520-6
56. Fojtik P, Vorlickova M. (2001). The fragile X chromosome (GCC) repeat folds into a DNA tetraplex at neutral pH. Nucleic Acids Res 29: 4684-90
57. Follonier C, Oehler J, Herrador R, Lopes M. (2013). Friedreich's ataxiaassociated GAA repeats induce replication-fork reversal and unusual molecular junctions. Nat Struct Mol Biol 20: 486-94
58. Fortune MT, Vassilopoulos C, Coolbaugh MI, et al. (2000). Dramatic, expansion-biased, age-dependent, tissue-specific somatic mosaicism in a transgenic mouse model of triplet repeat instability. Hum Mol Genet 9: 439-45
59. Fouche N, Ozgur S, Roy D, Griffith JD. (2006). Replication fork regression in repetitive DNAs. Nucleic Acids Res 34: 6044-50
60. Freudenreich CH, Kantrow SM, Zakian VA. (1998). Expansion and length-dependent fragility of CTG repeats in yeast. Science 279: 853-6
61. Freudenreich CH, Lahiri M. (2004). Structure-forming CAG/CTG repeat sequences are sensitive to breakage in the absence of Mrc1 checkpoint function and S-phase checkpoint signaling: implications for trinucleotide repeatexpansion diseases. Cell Cycle 3: 1370-4
62. Freudenreich CH, Stavenhagen JB, Zakian VA. (1997). Stability of a CTG/CAG trinucleotide repeat in yeast is dependent on its orientation in the genome. Mol Cell Biol 17: 2090-8
63. Frizzell A, Nguyen JH, Petalcorin MI, et al. (2014). RTEL1 inhibits trinucleotide repeatexpansions and fragility. Cell Rep 6: 827-35
64. Fry M, Loeb LA. (1994). The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. Proc Natl Acad Sci USA 91: 4950-4
65. Gacy AM, Goellner G, Juranic N, et al. (1995). Trinucleotide repeats thatexpand in human disease form hairpin structures in vitro. Cell 81: 533-40
66. Gangavarapu V, Prakash S, Prakash L. (2007). Requirement of RAD52 group genes for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol 27: 7758-64
67. Gannon AM, Frizzell A, Healy E, Lahue RS. (2012). MutSbeta and histone deacetylase complexes promote expansions of trinucleotide repeats in human cells. Nucleic Acids Res 40: 10324-33
68. Gao R, Matsuura T, Coolbaugh M, et al. (2008). Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17. Eur J Hum Genet 16: 215-22
69. Gatchel JR, Zoghbi HY. (2005). Diseases of unstable repeatexpansion: mechanisms and common principles. Nat Rev Genet 6: 743-55
70. Gellon L, Razidlo DF, Gleeson O, et al. (2011). New functions of Ctf18-RFC in preserving genome stability outside its role in sister chromatid cohesion. PLoS Genet 7: e1001298
71. Gerhardt J, Tomishima MJ, Zaninovic N, et al. (2014a). The DNA replication program is altered at the FMR1 locus in fragile X embryonic stem cells. Mol Cell 53: 19-31
72. Gerhardt J, Zaninovic N, Zhan Q, et al. (2014b). Cis-Acting DNA sequence at a replication origin promotes repeatexpansion to fragile X full mutation. J Cell Biol 206: 599-607
73. Gobbini E, Cesena D, Galbiati A, et al. (2013). Interplays between ATM/.Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks. DNA Repair (Amst) 12: 791-9
74. Gomes-Pereira M, Fortune MT, Ingram L, et al. (2004). Pms2 is a genetic enhancer of trinucleotide CAG.CTG repeat somatic mosaicism: implications for the mechanism of triplet repeatexpansion. Hum Mol Genet 13: 1815-25
75. Gomes-Pereira M, Hilley JD, Morales F, et al. (2014). Diseaseassociated CAG.CTG triplet repeats expand rapidlYin non-dividing mouse cells, but cell cycle arrest is insufficient to drive expansion. Nucleic Acids Res 42: 7047-56
76. Gonitel R, MoffitTh, Sathasivam K, et al. (2008). DNA instabilitYin postmitotic neurons. Proc Natl Acad Sci USA 105: 3467-72
77. Gorbunova V, Seluanov A, Mittelman D, Wilson JH. (2004). Genomewide demethylation destabilizes CTG.CAG trinucleotide repeats in mammalian cells. Hum Mol Genet 13: 2979-89
78. Goula AV, Berquist BR, Wilson III DM, et al. (2009). Stoichiometry of base excision repair proteins correlates with increased somatic CAG instabilitYin striatum over cerebellum in Huntington's disease transgenic mice. PLoS Genet 5: e1000749
79. Goula AV, Festenstein R, Merienne K. (2013). Tissue-dependent regulation of RNAP II dynamics: the missing link between transcription and trinucleotide repeat instabilitYin diseases?. Transcription 4: 172-6
80. Goula AV, Pearson CE, Della Maria J, et al. (2012a). The nucleotide sequence, DNA damage location, and protein stoichiometrYinfluence the base excision repair outcome at CAG/CTG repeats. Biochemistry 51: 3919-32
81. Goula AV, Stys A, Chan JP, et al. (2012b). Transcription elongation and tissue-specific somatic CAG instability. PLoS Genet 8: e1003051
82. Grabczyk E, Mancuso M, Sammarco MC. (2007). A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro. Nucleic Acids Res 35: 5351-9
83. Grabczyk E, Usdin K. (2000). The GAATTC triplet repeatexpanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner. Nucleic Acids Res 28: 2815-22
84. Grigg JC, Shumayrikh N, Sen D. (2014). G-quadruplex structures formed by expanded hexanucleotide repeat RNA and DNA from the neurodegenerative disease-linked c9orf72 gene efficiently sequester and activate heme. PLoS One 9: e106449
85. Groh M, Lufino MM, Wade-Martins R, Gromak N. (2014). R-loops associated with triplet repeatexpansions promote gene silencing in Friedreich ataxia and fragile X syndrome. PLoS Genet 10: e1004318
86. halabi A, Ditch S, Wang J, Grabczyk E. (2012). DNA mismatch repair complex MutSbeta promotes GAA.TTC repeatexpansion in human cells. J Biol Chem 287: 29958-67
87. hanawalt PC, Spivak G. (2008). Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 9: 958-70
88. hansen RS, Canfield TK, Fjeld AD, et al. (1997). A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spreaDof late replication. Proc Natl Acad Sci USA 94: 4587-92
89. hansen RS, Canfield TK, Lamb MM, et al. (1993). Association of fragile X syndrome with delayed replication of the FMR1 gene. Cell 73: 1403-9
90. hashimoto Y, Chaudhuri AR, Lopes M, Costanzo V. (2010). Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis. Nat Struct Mol Biol 17: 1305-11
91. hebert ML, Wells RD. (2005). Roles of double-strand breaks, nicks, and gaps in stimulating deletions of CTG.CAG repeats bYintramolecular DNA repair. J Mol Biol 353: 961-79
92. heidenfelder BL, Makhov AM, Topal MD. (2003). Hairpin formation in Friedreich's ataxia triplet repeatexpansion. J Biol Chem 278: 2425-31
93. heller RC, Marians KJ. (2006). Replication fork reactivation downstream of Ablocked nascent leading strand. Nature 439: 557-62
94. henricksen LA, Tom S, Liu Y, Bambara RA. (2000). Inhibition of flap endonuclease 1 by flap secondary structure and relevance to repeat sequence expansion. J Biol Chem 275: 16420-7
95. hicks WM, Kim M, Haber JE. (2010). Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329: 82-5
96. hohl M, Thorel F, Clarkson SG, Scharer OD. (2003). Structural determinants for substrate binding and catalysis by the structurespecific endonuclease XPG. J Biol Chem 278: 19500-8
97. hou C, Zhang T, Tian L, et al. (2011). The role of XPG in processing (CAG)n/(CTG)n DNA hairpins. Cell Biosci 1: 11
98. house NC, Koch MR, Freudenreich CH. (2014a). Chromatin modifications and DNA repair: beyond double-strand breaks. Front Genet 5: Article 296
99. house NC, Yang JH, Walsh SC, et al. (2014b). NuA4 initiates dynamic histone H4 acetylation to promote high-fidelity sister chromatid recombination at postreplication gaps. Mol Cell 55: 818-28
100. huber MD, Lee DC, Maizels N. (2002). G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific inhibition. Nucleic Acids Res 30: 3954-61
101. hubert Jr L, Lin Y, Dion V, Wilson JH. (2011). Xpa deficiency reduces CAG trinucleotide repeat instabilitYin neuronal tissues in a mouse model of SCA1. Hum Mol Genet 20: 4822-30
102. Imbert G, Saudou F, Yvert G, et al. (1996). Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 14: 285-91
103. Ira G, Haber JE. (2002). Characterization of RAD51-independent breakinduced replication that acts preferentially with shorThomologous sequences. Mol Cell Biol 22: 6384-92
104. Iraqui I, Chekkal Y, Jmari N, et al. (2012). Recovery of arrested replication forks by homologous recombination is error-prone. PLoS Genet 8: e1002976
105. Jalal SM, Lindor NM, Michels VV, et al. (1993). Absence of chromosome fragility at 19q13.3 in patients with myotonic dystrophy. Am J Med Genet 46: 441-3
106. Jankowski C, Nasar F, Nag DK. (2000). Meiotic instability of CAG repeat tracts occurs by double-strand break repair in yeast. Proc Natl Acad Sci USA 97: 2134-9
107. Jarem DA, Wilson NR, Delaney S. (2009). Structure-dependent DNA damage and repair in a trinucleotide repeat sequence. Biochemistry 48: 6655-63
108. Jarem DA, Wilson NR, Schermerhorn KM, Delaney S. (2011). Incidence and persistence of 8-oxo-7,8-dihydroguanine within a hairpin intermediate exacerbates a toxic oxidation cycle associated with trinucleotide repeatexpansion. DNA Repair (Amst) 10: 887-96
109. Javeri A, Lyons JG, Huang XX, Halliday GM. (2011). Downregulation of Cockayne syndrome B protein reduces human 8-oxoguanine DNA glycosylase-1 expression and repair of UV radiation-induced 8-oxo-7,8-dihydro-20-deoxyguanine. Cancer Sci 102: 1651-8
110. Jeffreys AJ, Tamaki K, MacLeod A, et al. (1994). Complex gene conversion events in germline mutation aThuman minisatellites. Nat Genet 6: 136-45
111. Jung J, Bonini N. (2007). CREB-binding protein modulates repeat instabilitYin a Drosophila model for polyQ disease. Science 315: 1857-9
112. Kadyrov FA, Genschel J, Fang Y, et al. (2009). A possible mechanism for exonuclease 1-independenteukaryotic mismatch repair. Proc Natl Acad Sci USA 106: 8495-500
113. Kang S, Jaworski A, Ohshima K, Wells RD. (1995). Expansion and deletion of CTG repeats from human disease genes are determined by the direction of replication in E. coli. Nat Genet 10: 213-18
114. Kantartzis A, Williams GM, Balakrishnan L, et al. (2012). Msh2-Msh3 interferes with Okazaki fragment processing to promote trinucleotide repeatexpansions. Cell Rep 2: 216-22
115. Katou Y, Kanoh Y, Bando M, et al. (2003). S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Nature 424: 1078-83
116. Kennedy L, Evans E, Chen CM, et al. (2003). Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis. Hum Mol Genet 12: 3359-67
117. Kerrest A, Anand RP, Sundararajan R, et al. (2009). SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination. Nat Struct Mol Biol 16: 159-67
118. Kettani A, Kumar RA, Patel DJ. (1995). Solution structure of a DNA quadruplex containing the fragile X syndrome triplet repeat. J Mol Biol 254: 638-56
119. Kim HM, Narayanan V, Mieczkowski PA, et al. (2008). Chromosome fragility at GAA tracts in yeast depends on repeat orientation and requires mismatch repair. EMBO J 27: 2896-906
120. Kim JC, Mirkin SM. (2013). The balancing act of DNA repeatexpansions. Curr Opin Genet Dev 23: 280-8
121. Kovalenko M, Dragileva E, St Claire J, et al. (2012). Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutanThuntingtin phenotypes in huntington's disease knock-in mice. PLoS One 7: e44273. doi: 10.1371/journal.pone.0044273
122. Kovtun IV, Johnson KO, McMurray CT. (2011). Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo. Aging 3: 509-14
123. Kovtun IV, Liu Y, Bjoras M, et al. (2007). OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature 447: 447-52
124. Kovtun IV, McMurray CT. (2001). Trinucleotide expansion in haploid germ cells by gap repair. Nat Genet 27: 407-11
125. Kovtun IV, Thornhill AR, McMurray CT. (2004). Somatic deletion events occur during early embryonic development and modify the extent of CAG expansion in subsequent generations. Human Mol Genet 13: 3057-68
126. Krasilnikova MM, Kireeva ML, Petrovic V, et al. (2007). Effects of Friedreich's ataxia (GAA)n (TTC)n repeats on RNA synthesis and stability. Nucleic Acids Res 35: 1075-84
127. Krasilnikova MM, Mirkin SM. (2004). Replication stalling at Friedreich's ataxia (GAA)n repeats in vivo. Mol Cell Biol 24: 2286-95
128. Ku S, Soragni E, Campau E, et al. (2010). Friedreich's ataxia induced pluripotent stem cells model intergenerational GAATTC triplet repeat instability. Cell Stem Cell 7: 631-7
129. Kumari D, Usdin K. (2009). Chromatin remodeling in the noncoding repeatexpansion diseases. J Biol Chem 284: 7413-17
130. La Spada AR, Wilson EM, Lubahn DB, et al. (1991). Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 77-9
131. Ladd PD, Smith LE, Rabaia NA, et al. (2007). An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals. Hum Mol Genet 16: 3174-87
132. Lahiri M, Gustafson TL, Majors ER, Freudenreich CH. (2004). Expanded CAG repeats activate the DNA damage checkpoint pathway. Mol Cell 15: 287-93
133. Lai Y, Beaver JM, Lorente K, et al. (2014). Base excision repair of chemotherapeutically-induced alkylated DNA damage predominantly causes contractions of expanded GAA repeats associated with Friedreich's ataxia. PLoS One 9: e93464
134. Lai Y, Xu M, Zhang Z, Liu Y. (2013). Instability of CTG repeats is governed by the position of a DNAbase lesion through base excision repair. PLoS One 8: e56960
135. Lam EY, Beraldi D, Tannahill D, Balasubramanian S. (2013). G-quadruplex structures are stable and detectable in human genomic DNA. Nat Commun 4: Article no. 1796
136. Lang WH, Coats JE, Majka J, et al. (2011). Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops. Proc Natl Acad Sci USA 108: E837-44
137. Lia AS, Seznec H, Hofmann-Radvanyi H, et al. (1998). Somatic instability of the CTG repeat in mice transgenic for the myotonic dystrophy region is age dependent but not correlated to the relative intertissue transcription levels and proliferative capacities. Hum Mol Genet 7: 1285-91
138. Libby RT, Hagerman KA, Pineda VV, et al. (2008). CTCF cis-regulates trinucleotide repeat instabilitYin an epigenetic manner: a novel basis for mutational hot spot determination. PLoS Genet 4: e1000257
139. Libby RT, Monckton DG, Fu Y-H, et al. (2003). Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice. Hum Mol Genet 12: 41-50
140. Lieber MR. (2010). NHEJ and its backup pathways in chromosomal translocations. Nat Struct Mol Biol 17: 393-5
141. Lin Y, Dent SY, Wilson JH, et al. (2010a). R loops stimulate genetic instability of CTG.CAG repeats. Proc Natl Acad Sci USA 107: 692-7
142. Lin Y, Dion V, Wilson JH. (2006). Transcription promotes contraction of CAG repeat tracts in human cells. Nat Struct Mol Biol 13: 179-80
143. Lin Y, Hubert Jr L, Wilson JH. (2009). Transcription destabilizes triplet repeats. Mol Carcinog 48: 350-61
144. Lin Y, Leng M, Wan M, Wilson JH. (2010b). Convergent transcription through a long CAG tract destabilizes repeats and induces apoptosis. Mol Cell Biol 18: 4435-51
145. Lin Y, Wilson JH. (2007). Transcription-induced CAG repeat contraction in human cells is mediated in part by transcription-coupled nucleotide excision repair. Mol Cell Biol 27: 6209-17
146. Lin Y, Wilson JH. (2012). Nucleotide excision repair, mismatch repair, and R-loops modulate convergent transcription-induced cell death and repeat instability. PLoS One 7: e46807
147. Liquori CL, Ikeda Y, Weatherspoon M, et al. (2003). Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract. Am J Hum Genet 73: 849-62
148. Liu G, Chen X, Bissler JJ, et al. (2010). Replication-dependent instability at (CTG) x (CAG) repeaThairpins in human cells. Nat Chem Biol 6: 652-9
149. Liu G, Leffak M. (2012). Instability of (CTG)n (CAG)n trinucleotide repeats and DNA synthesis. Cell Biosci 2: 7
150. Liu Y, Bambara RA. (2003). Analysis of human flap endonuclease 1 mutants reveals a mechanism to prevent triplet repeatexpansion. J Biol Chem 278: 13728-39
151. Liu Y, Beard WA, Shock DD, et al. (2005). DNA polymerase beta and flap endonuclease 1 enzymatic specificities sustain DNA synthesis for long patch base excision repair. J Biol Chem 280: 3665-74
152. Liu Y, Prasad R, Beard WA, et al. (2009). Coordination between Pol beta and FEN1 can modulate CAG repeatexpansion. J Biol Chem 284: 28352-66
153. Liu Y, Wilson SH. (2012). DNAbase excision repair: a mechanism of trinucleotide repeatexpansion. Trends Biochem Sci 37: 162-72
154. Liu Y, Zhang H, Veeraraghavan J, et al. (2004). Saccharomyces cerevisiae flap endonuclease 1 uses flap equilibration to maintain triplet repeat stability. Mol Cell Biol 24: 4049-64
155. Lobachev KS, Gordenin DA, Resnick MA. (2002). The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements. Cell 108: 183-93
156. Loesch D, Hagerman R. (2012). Unstable mutations in the FMR1 gene and the phenotypes. Adv Exp Med Biol 769: 78-114
157. Lokanga RA, Entezam A, Kumari D, et al. (2013). Somatic expansion in mouse and human carriers of Fragile X premutation alleles. Hum Mutat 34: 157-66
158. Lokanga RA, Zhao XN, Entezam A, Usdin K. (2014a). X inactivation plays a major role in the gender bias in somatic expansion in a mouse model of the Fragile X-related disorders: implications for the mechanism of repeatexpansion. Hum Mol Genet 23: 4985-94
159. Lokanga RA, Zhao X-N, Usdin K. (2014b). The mismatch repair protein, MSH2, is rate-limiting for repeatexpansion in a Fragile X premutation mouse model. Hum Mutat 35: 129-36
160. Loomis EW, Sanz LA, Chedin F, Hagerman PJ. (2014). Transcriptionassociated R-loop formation across the human FMR1 CGG-repeat region. PLoS Genet 10: e1004294
161. Lopez Castel A, Cleary JD, Pearson CE. (2010). Repeat instability as the basis for human diseases and as a potential target for therapy. Nat Rev Mol Cell Biol 11: 165-70
162. Lopez Castel A, Nakamori M, Tome S, et al. (2011). Expanded CTG repeat demarcates Aboundary for abnormal CpG methylation in myotonic dystrophy patient tissues. Hum Mol Genet 20: 1-15
163. Lou H, Komata M, Katou Y, et al. (2008). Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint. Mol Cell 32: 106-17
164. MacDougall CA, Byun TS, Van C, et al. (2007). The structural determinants of checkpoint activation. Genes Dev 21: 898-903
165. Mangiarini L, Sathasivam K, Mahal A, et al. (1997). Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. Nat Genet 15: 197-200
166. Manley K, Shirley TL, Flaherty L, Messer A. (1999). Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice. Nat Genet 23: 471-3
167. Mariappan SV, Silks 3rd LA, Chen X, et al. (1998). Solution structures of the Huntington's disease DNA triplets, (CAG)n. J Biomol Struct Dyn 15: 723-44
168. Martins S, Coutinho P, Silveira I, et al. (2008). Cis-Acting factors promoting the CAG intergenerational instabilitYin Machado-Joseph disease. Am J Med Genet B Neuropsychiatr Genet: Official Publ Int Soc Psychiatric Genet 147b: 439-46
169. Martins S, Pearson CE, Coutinho P, et al. (2014). Modifiers of (CAG)n instabilitYin Machado-Joseph disease (MJD/SCA3) transmissions: an association study with DNA replication, repair and recombination genes. Hum Genet 133: 1311-18
170. Mason AG, Tome S, Simard JP, et al. (2014). Expression levels of DNA replication and repair genes predict regional somatic repeat instabilitYin the brain but are not altered by polyglutamine disease protein expression or age. Hum Mol Genet 23: 1606-18
171. Matsuura T, Yamagata T, Burgess DL, et al. (2000). Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 26: 191-4
172. Maurer DJ, O'Callaghan BL, Livingston DM. (1996). Orientation dependence of trinucleotide CAG repeat instabilitYin Saccharomyces cerevisiae. Mol Cell Biol 16: 6617-22
173. McMurray CT. (2008). Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease. DNA Repair (Amst) 7: 1121-34
174. McMurray CT. (2010). Mechanisms of trinucleotide repeat instability during human development. Nat Rev Genet 11: 786-99
175. McVey M, Lee SE. (2008). MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings. Trends Genet 24: 529-38
176. Mimitou EP, Symington LS. (2011). DNA end resection-unraveling the tail. DNA Repair (Amst) 10: 344-8
177. Minca EC, Kowalski D. (2010). Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks. Mol Cell 38: 649-61
178. Miret JJ, Pessoa-Brandao L, Lahue RS. (1998). Orientation-dependent and sequence-specific expansions of CTG/CAG trinucleotide repeats in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 95: 12438-43
179. Mirkin EV, Mirkin SM. (2014). To switch or not to switch: at the origin of repeatexpansion disease. Mol Cell 53: 1-3
180. Mirkin SM. (2006). DNA structures, repeatexpansions and human hereditary disorders. Curr Opin Struct Biol 16: 351-8
181. Mirkin SM, Smirnova EV. (2002). Positioned to expand. Nat Genet 31: 5-6
182. Mitas M, Yu A, Dill J, Haworth IS. (1995a). The trinucleotide repeat sequence d(CGG)15 forms a heat-stable hairpin containing Gsyn. Ganti base pairs. Biochemistry 34: 12803-11
183. Mitas M, Yu A, Dill J, et al. (1995b). Hairpin properties of singlestranded DNA containing a GC-rich triplet repeat: (CTG)15. Nucleic Acids Res 23: 1050-9
184. Mittelman D, Moye C, Morton J, et al. (2009). Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instabilitYin human cells. Proc Natl Acad Sci USA 106: 9607-12
185. Modrich P. (2006). Mechanisms in eukaryotic mismatch repair. J Biol Chem 281: 30305-9
186. Moldovan GL, Dejsuphong D, Petalcorin MI, et al. (2012). Inhibition of homologous recombination by the PCNA-interacting protein PARI. Mol Cell 45: 75-86
187. Mollersen L, Rowe AD, Illuzzi JL, et al. (2012). Neil1 is a genetic modifier of somatic and germline CAG trinucleotide repeat instabilitYin R6/1 mice. Hum Mol Genet 21: 4939-47
188. Monckton DG, Caskey CT. (1995). Unstable triplet repeat diseases. Circulation 91: 513-20
189. Morales F, Couto JM, Higham CF, et al. (2012). Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity. Hum Mol Genet 21: 3558-67
190. Morales F, Vasquez M, Cuenca P, et al. (2014). Parental age effects, but no evidence for an intrauterine effect in the transmission of myotonic dystrophy type 1. Eur J Hum Genet [Epub aheaDof print]. doi: 10.1038/ejhg.2014.138
191. Moseley ML, Zu T, Ikeda Y, et al. (2006). Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet 38: 758-69
192. Mott C, Symington LS. (2011). RAD51-independent inverted-repeat recombination by a strand-Annealing mechanism. DNA Repair (Amst)10: 408-15
193. Mozlin AM, Fung CW, Symington LS. (2008). Role of the Saccharomyces cerevisiae Rad51 paralogs in sister chromatid recombination. Genetics 178: 113-26
194. Muftuoglu M, de Souza-Pinto NC, Dogan A, et al. (2009). Cockayne syndrome group B protein stimulates repair of formamidopyrimidines by NEIL1 DNA glycosylase. J Biol Chem 284: 9270-9
195. Muftuoglu M, Sharma S, Thorslund T, et al. (2006). Cockayne syndrome group B protein has novel strand annealing and exchange activities. Nucleic Acids Res 34: 295-304
196. Mulvihill DJ, Nichol Edamura K, Hagerman KA, et al. (2005). Effect of CAT or AGG interruptions and CpG methylation on nucleosome assembly upon trinucleotide repeats on spinocerebellar ataxia, type 1 and fragile X syndrome. J Biol Chem 280: 4498-503
197. Murray A, Ennis S, Youings SA, et al. (2000). Stability and haplotype analysis of the FRAXE region. Eur J Hum Genet 8: 583-9
198. Nadel Y, Weisman-Shomer P, Fry M. (1995). The fragile X syndrome single strand d(CGG)n nucleotide repeats readily fold back to form unimolecular hairpin structures. J Biol Chem 270: 28970-7
199. Nag DK, Suri M, Stenson EK. (2004). Both CAG repeats and inverted DNA repeats stimulate spontaneous unequal sister-chromatid exchange in Saccharomyces cerevisiae. Nucleic Acids Res 32: 5677-84
200. Nakamori M, Pearson CE, Thornton CA. (2011). Bidirectional transcription stimulates expansion and contraction of expanded (CTG) (CAG) repeats. Hum Mol Genet 20: 580-8
201. Napierala M, Parniewski P, Pluciennik A, Wells RD. (2002). Long CTG.CAG repeat sequences markedly stimulate intramolecular recombination. J Biol Chem 277: 34087-100
202. Naylor ML, Li JM, Osborn AJ, Elledge SJ. (2009). Mrc1 phosphorylation in response to DNA replication stress is required for Mec1 accumulation at the stalled fork. Proc Natl Acad Sci USA 106: 12765-70
203. Nestor CE, Monckton DG. (2011). Correlation of inter-locus polyglutamine toxicity with CAG CTG triplet repeatexpandability and flanking genomic DNA GC content. PLoS One 6: e28260
204. Neville CE, Mahadevan MS, Barcelo JM, Korneluk RG. (1994). High resolution genetic analysis suggests one ancestral predisposing haplotype for the origin of the myotonic dystrophy mutation. Hum Mol Genet 3: 45-51
205. Nolin SL, Glicksman A, Ding X, et al. (2011). Fragile X analysis of 1112 prenatal samples from 1991 to 2010. Prenat Diagn 31: 925-31
206. Nolin SL, Sah S, Glicksman A, et al. (2013). Fragile X AGG analysis provides new risk predictions for 45-69 repeat alleles. Am J Med Genet A 161A: 771-8
207. Northam MR, Moore EA, Mertz TM, et al. (2014). DNA polymerases zeta and Rev1 mediate error-prone bypass of non-B DNA structures. Nucleic Acids Res 42: 290-306
208. Oberle I, Rousseau F, Heitz D, et al. (1991). Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252: 1097-102
209. Owen BA, Lang WH, McMurray CT. (2009). The nucleotide binding dynamics of human MSH2-MSH3 are lesion dependent. Nat Struct Mol Biol 16: 550-7
210. Owen BA, Yang Z, Lai M, et al. (2005). (CAG)(n)-hairpin DNAbinds to Msh2-Msh3 and changes properties of mismatch recognition. Nat Struct Mol Biol 12: 663-70
211. Panigrahi GB, Cleary JD, Pearson CE. (2002). In vitro (CTG) (CAG) expansions and deletions by human cell extracts. J Biol Chem 277: 13926-34
212. Panigrahi GB, Lau R, Montgomery SE, et al. (2005). Slipped (CTG) (CAG) repeats can be correctly repaired, escape repair or undergo error-prone repair. Nat Struct Mol Biol 12: 654-62
213. Panigrahi GB, Slean MM, Simard JP, et al. (2010). Isolated short CTG/.CAG DNA slip-outs are repaired efficiently by hMutSbeta, but clustered slip-outs are poorly repaired. Proc Natl Acad Sci USA 107: 12593-8
214. Pearson CE, Edamura KN, Cleary JD. (2005). Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet 6: 729-42
215. Pearson CE, Wang YH, Griffith JD, Sinden RR. (1998). Structural analysis of slipped-strand DNA (S-DNA) formed in (CTG) n.(CAG) n repeats from the myotonic dystrophy locus. Nucleic Acids Res 26: 816-23
216. Pelletier R, Krasilnikova MM, Samadashwily GM, et al. (2003). Replication and expansion of trinucleotide repeats in yeast. Mol Cell Biol 23: 1349-57
217. Pinto RM, Dragileva E, Kirby A, et al. (2013). Mismatch repair genes Mlh1 and Mlh3 modify CAG instabilitYin Huntington's disease mice: genome-wide and candidate approaches. PLoS Genet 9: e1003930
218. Pluciennik A, Burdett V, Baitinger C, et al. (2013). Extrahelical (CAG)/.(CTG) triplet repeatelements support proliferating cell nuclear antigen loading and MutLalpha endonuclease activation. Proc Natl Acad Sci USA 110: 12277-82
219. Pluciennik A, Iyer RR, Napierala M, et al. (2002). Long CTG.CAG repeats from myotonic dystrophy are preferred sites for intermolecular recombination. J Biol Chem 277: 34074-86
220. Potaman VN, Bissler JJ, Hashem VI, et al. (2003). Unpaired structures in SCA10 (ATTCT)n.(AGAAT)n repeats. J Mol Biol 326: 1095-111
221. Potaman VN, Oussatcheva EA, Lyubchenko YL, et al. (2004). Lengthdependent structure formation in Friedreich ataxia (GAA)n (TTC)n repeats at neutral pH. Nucleic Acids Res 32: 1224-31
222. Prado F, Aguilera A. (1995). Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes. Genetics 139: 109-23
223. Ranjha L, Anand R, Cejka P. (2014). The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions. J Biol Chem 289: 5674-86
224. Razidlo DF, Lahue RS. (2008). Mrc1, Tof1 and Csm3 inhibit CAG.CTG repeat instability by at least two mechanisms. DNA Repair (Amst) 7: 633-40
225. Reddy K, Schmidt MH, Geist JM, et al. (2014). Processing of double-Rloops in (CAG).(CTG) and C9orf72 (GGGGCC).(GGCCCC) repeats causes instability. Nucleic Acids Res 42: 10473-87
226. Reddy K, Tam M, Bowater RP, et al. (2011). Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats. Nucleic Acids Res 39: 1749-62
227. Renton AE, Majounie E, Waite A, et al. (2011). A hexanucleotide repeatexpansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72: 257-68
228. Richard GF, Dujon B, Haber JE. (1999). Double-strand break repair can lead to high frequencies of deletions within short CAG/CTG trinucleotide repeats. Mol Gen Genet 261: 871-82
229. Richard GF, Goellner GM, McMurray CT, Haber JE. (2000). Recombination-induced CAG trinucleotide repeatexpansions in yeast involve the MRE11-RAD50-XRS2 complex. EMBO J 19: 2381-90
230. Richard GF, Viterbo D, Khanna V, et al. (2014). Highly specific contractions of a single CAG/CTG trinucleotide repeat by TALEN in yeast. PLoS One 9: e95611
231. Richards RI, Holman K, Friend K, et al. (1992). Evidence of founder chromosomes in fragile X syndrome. Nat Genet 1: 257-60
232. Richards RI, Sutherland GR. (1994). Simple repeat DNA is not replicated simply. Nat Genet 6: 114-16
233. Roesner LM, Mielke C, Fahnrich S, et al. (2013). Stable expression of MutLgamma in human cells reveals no specific response to mismatched DNA, but distinct recruitment to damage sites. J Cell Biochem 114: 2405-14
234. Rolfsmeier ML, Dixon MJ, Pessoa-Brandao L, et al. (2001). Ciselements governing trinucleotide repeat instabilitYin Saccharomyces cerevisiae. Genetics 157: 1569-79
235. Saha T, Usdin K. (2001). Tetraplex formation by the progressive myoclonus epilepsy type-1 repeat: implications for instabilitYin the repeatexpansion diseases. FEBS Lett 491: 184-7
236. Saini N, Zhang Y, Nishida Y, et al. (2013). Fragile DNA motifs trigger mutagenesis at distant chromosomal loci in Saccharomyces cerevisiae. PLoS Genet 9: e1003551
237. Sakamoto N, Larsonje, Iyer RR, et al. (2001). GGA TCC-interrupted triplets in long GAA TTC repeats inhibit the formation of triplex and sticky DNA structures, alleviate transcription inhibition, and reduce genetic instabilities. J Biol Chem 276: 27178-87
238. Salinas-Rios V, Belotserkovskii BP, Hanawalt PC. (2011). DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability. Nucleic Acids Res 39: 7444-54
239. Saugar I, Ortiz-Bazan MA, Tercero JA. (2014). Tolerating DNA damage during eukaryotic chromosome replication. Exp Cell Res 329: 170-7
240. Savouret C, Brisson E, Essers J, et al. (2003). CTG repeat instability and size variation timing in DNA repair-deficient mice. EMBO J 22: 2264-73
241. Savouret C, Garcia-Cordier C, Megret J, et al. (2004). MSH2-dependent germinal CTG repeatexpansions are produced continuouslYin spermatogonia from DM1 Transgenic Mice. Mol Cell Biol 24: 629-37
242. Schweitzer JK, Livingston DM. (1997). Destabilization of CAG trinucleotide repeat tracts by mismatch repair mutations in yeast. Hum Mol Genet 6: 349-55
243. Schweitzer JK, Livingston DM. (1999). The effect of DNA replication mutations on CAG tract stabilitYin yeast. Genetics 152: 953-63
244. Schweitzer JK, Reinke SS, Livingston DM. (2001). Meiotic alterations in CAG repeat tracts. Genetics 159: 1861-5
245. Seriola A, Spits C, Simard JP, et al. (2011). Huntington's and myotonic dystrophy hESCs: down-regulated trinucleotide repeat instability and mismatch repair machinery expression upon differentiation. Hum Mol Genet 20: 176-85
246. Shah KA, McGinty RJ, Egorova VI, Mirkin SM. (2014). Coupling transcriptional state to large-scale repeatexpansions in yeast. Cell Rep 9: 1594-602
247. Shah KA, Shishkin AA, Voineagu I, et al. (2012). Role of DNA polymerases in repeat-mediated genome instability. Cell Rep 2: 1088-95
248. Shen J, Loeb LA. (2001). Unwinding the molecular basis of the Werner syndrome. Mech Ageing Dev 122: 921-44
249. Shishkin AA, Voineagu I, Matera R, et al. (2009). Large-scale expansions of Friedreich's ataxia GAA repeats in yeast. Mol Cell 35: 82-92
250. Shrivastav M, De Haro LP, Nickoloff JA. (2008). Regulation of DNA double-strand break repair pathway choice. Cell Res 18: 134-47
251. SimarDo, Gregoire MC, Arguin M, et al. (2014). Instability of trinucleotidic repeats during chromatin remodeling in spermatids. Hum Mutat 35: 1280-4
252. Sopher BL, Ladd PD, Pineda VV, et al. (2011). CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA. Neuron 70: 1071-84
253. Spiro C, McMurray CT. (2003). Nuclease-deficient FEN-1 blocks Rad51/BRCA1-mediated repair and causes trinucleotide repeat instability. Mol Cell Biol 23: 6063-74
254. Spiro C, Pelletier R, Rolfsmeier ML, et al. (1999). Inhibition of FEN-1 processing by DNA secondary structure at trinucleotide repeats. Mol Cell 4: 1079-85
255. Staresincic L, Fagbemi AF, Enzlin JH, et al. (2009). Coordination of dual incision and repair synthesis in human nucleotide excision repair. EMBO J 28: 1111-20
256. Subramanian PS, Nelson DL, Chinault AC. (1996). Large domains of apparent delayed replication timing associated with triplet repeatexpansion at FRAXA and FRAXE. Am J Hum Genet 59: 407-16
257. Sun H, Karow JK, Hickson ID, Maizels N. (1998). The Bloom's syndrome helicase unwinds G4 DNA. J Biol Chem 273: 27587-92
258. Sundararajan R, Freudenreich CH. (2011). Expanded CAG/CTG repeat DNA induces a checkpoint response that impacts cell proliferation in Saccharomyces cerevisiae. PLoS Genet 7: e1001339
259. Sundararajan R, Gellon L, Zunder RM, Freudenreich CH. (2010). Double-strand break repair pathways protect against CAG/CTG repeatexpansions, contractions and repeat-mediated chromosomal fragilitYin Saccharomyces cerevisiae. Genetics 184: 65-77
260. Suwaki N, Klare K, Tarsounas M. (2011). RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol 22: 898-905
261. Symington LS, Gautier J. (2011). Double-strand break end resection and repair pathway choice. Annu Rev Genet 45: 247-71
262. Takiyama Y, Igarashi S, Rogaeva EA, et al. (1995). Evidence for intergenerational instabilitYin the CAG repeat in the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease. Hum Mol Genet 4: 1137-46
263. Tang W, Dominska M, Greenwell PW, et al. (2011). Friedreich's ataxia (GAA)n (TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae. PLoS Genet 7: e1001270
264. Tang W, Dominska M, Gawel M, et al. (2013). Genomic deletions and point mutations induced in Saccharomyces cerevisae by the trinucleotide repeats (GAA.TTC) associated with Friedreich's ataxia. DNA Repair 12: 10-17
265. Tian L, Hou C, Tian K, et al. (2009). Mismatch recognition protein MutSbeta does noThijack (CAG)n hairpin repair in vitro. J Biol Chem 284: 20452-6
266. Tittel-Elmer M, Alabert C, Pasero P, Cobb JA. (2009). The MRX complex stabilizes the replisome independently of the S phase checkpoint during replication stress. EMBO J 28: 1142-56
267. Tome S, Holt I, Edelmann W, et al. (2009). MSH2 ATPase domain mutation affects CTG CAG repeat instabilitYin transgenic mice. PLoS Genet 5: e1000482. doi: 10.1371/journal.pgen.1000482
268. Tome S, Manley K, Simard JP, et al. (2013). MSH3 polymorphisms and protein levels affect CAG repeat instabilitYin Huntington's disease mice. PLoS Genet 9: e1003280
269. Tourriere H, Versini G, Cordon-Preciado V, et al. (2005). Mrc1 and Tof1 promote replication fork progression and recoverYindependently of Rad53. Mol Cell 19: 699-706
270. Tuo J, Chen C, Zeng X, et al. (2002). Functional crosstalk between hOgg1 and the helicase domain of Cockayne syndrome group B protein. DNA Repair (Amst) 1: 913-27
271. Usdin K, Woodford KJ. (1995). CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro. Nucleic Acids Res 23: 4202-9
272. van den Broek WJ, Nelen MR, van der Heijden GW, et al. (2006). Fen1 does not control somatic hypermutability of the (CTG)(n) (CAG)(n) repeat in a knock-in mouse model for DM1. FEBS Lett 580: 5208-14
273. van Veelen LR, Essers J, van de Rakt MW, et al. (2005). Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52. Mutat Res 574: 34-49
274. Vannier JB, Pavicic-Kaltenbrunner V, Petalcorin MI, et al. (2012). RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell 149: 795-806
275. Vannier JB, Sandhu S, Petalcorin MI, et al. (2013). RTEL1 is a replisome-Associated helicase that promotes telomere and genomewide replication. Science 342: 239-42
276. Vanoli F, Fumasoni M, Szakal B, et al. (2010). Replication and recombination factors contributing to recombination-dependent bypass of DNA lesions by template switch. PLoS Genet 6: e1001205
277. Verkerk AJ, Pieretti M, Sutcliffe JS, et al. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with Abreakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65: 905-14
278. Voineagu I, Freudenreich CH, Mirkin SM. (2009a). Checkpoint responses to unusual structures formed by DNA repeats. Mol Carcinog 48: 309-18
279. Voineagu I, Surka CF, Shishkin AA, et al. (2009b). Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility. Nat Struct Mol Biol 16: 226-8
280. Wang G, Christensen LA, Vasquez KM. (2006). Z-DNA-forming sequences generate large-scale deletions in mammalian cells. Proc Natl Acad Sci USA 103: 2677-82
281. Wang G, Vasquez KM. (2004). Naturally occurring H-DNA-forming sequences are mutagenic in mammalian cells. Proc Natl Acad Sci USA 101: 13448-53
282. Wang G, Vasquez KM. (2009). Models for chromosomal replicationindependent non-B DNA structure-induced genetic instability. Mol Carcinog 48: 286-98
283. Warby SC, Montpetit A, Hayden AR, et al. (2009). CAG expansion in the Huntington disease gene is associated with a specific and targetable predisposing haplogroup. Am J Hum Genet 84: 351-66
284. Watanabe H, Tanaka F, Doyu M, et al. (2000). Differential somatic CAG repeat instabilitYin variable brain cell lineage in dentatorubral pallidoluysian atrophy (DRPLA): a laser-captured microdissection (LCM)-based analysis. Hum Genet 107: 452-7
285. Wenger SL, Giangreco CA, Tarleton J, Wessel HB. (1996). Inability to induce fragile sites at CTG repeats in congenital myotonic dystrophy. Am J Hum Genet 66: 60-3
286. Wheeler VC, Lebel LA, Vrbanac V, et al. (2003). Mismatch repair gene Msh2 modifies the timing of early disease in hdh(Q111) striatum. Human Mol Genet 12: 273-81
287. Williams RS, Williams JS, Tainer JA. (2007). Mre11-Rad50-Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin template. Biochem Cell Biol 85: 509-20
288. Wohrle D, Salat U, Hameister H, et al. (2001). Demethylation, reactivation, and destabilization of human fragile X full-mutation alleles in mouse embryocarcinoma cells. Am J Hum Genet 69: 504-15
289. Xu M, Gabison J, Liu Y. (2013). Trinucleotide repeat deletion via a unique hairpin bypass by DNA polymerase beta and alternate flap cleavage by flap endonuclease 1. Nucleic Acids Res 41: 1684-97
290. Xu M, Lai Y, Torner J, et al. (2014). Base excision repair of oxidative DNA damage coupled with removal of a CAG repeaThairpin attenuates trinucleotide repeatexpansion. Nucleic Acids Res 42: 3675-91
291. Yang J, Freudenreich CH. (2007). Haploin sufficiency of yeast FEN1 causes instability of expanded CAG/CTG tracts in a length-dependent manner. Gene 393: 110-15
292. Yang JH, Freudenreich CH. (2010). The Rtt109 histone acetyltransferase facilitates error-free replication to prevent CAG/CTG repeat contractions. DNA Repair (Amst) 9: 414-20
293. Yoon SR, Dubeau L, de Young M, et al. (2003). Huntington disease expansion mutations in humans can occur before meiosis is completed. Proc Natl Acad Sci USA 100: 8834-8
294. Yrigollen CM, Durbin-Johnson B, Gane L, et al. (2012). AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genet Med 14: 729-36
295. Yrigollen CM, Martorell L, Durbin-Johnson B, et al. (2014). AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission. J Neurodev Disord 6: 24
296. Yu A, Barron MD, Romero RM, et al. (1997). At physiological pH, d(CCG)15 forms a hairpin containing protonated cytosines and a distorted helix. Biochemistry 36: 3687-99
297. Yu S, Pritchard M, Kremer E, et al. (1991). Fragile X genotype characterized by an unstable region of DNA. Science 252: 1179-81
298. Yudkin D, Hayward BE, Aladjem MI, et al. (2014). Chromosome fragility and the abnormal replication of the FMR1 locus in Fragile X syndrome. Hum Mol Genet 23: 2940-52
299. Zatz M, Passos-Bueno MR, Cerqueira A, et al. (1995). Analysis of the CTG repeat in skeletal muscle of young and adult myotonic dystrophy patients: when does the expansion occur?. Hum Mol Genet 4: 401-6
300. Zegerman P, Diffley JF. (2009). DNA replication as a target of the DNA damage checkpoint. DNA Repair (Amst) 8: 1077-88
301. Zhang H, Lawrence CW. (2005). The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of budding yeastemploys sister-strand recombination. Proc Natl Acad Sci USA 102: 15954-9
302. Zhang T, Huang J, Gu L, Li GM. (2012a). In vitro repair of DNA hairpins containing various numbers of CAG/CTG trinucleotide repeats. DNA Repair (Amst) 11: 201-9
303. Zhang Y, Shishkin AA, Nishida Y, et al. (2012b). Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and expansions in dividing and nondividing yeast cells. Mol Cell 48: 254-65
304. Zhao X-N, Usdin K. (2014). Gender and cell-Type specific effects of the transcription coupled repair protein, ERCC6/CSB, on repeatexpansion in a mouse model of the Fragile X-related disorders. Hum Mutat 35: 341-9
305. Zlatanou A, Despras E, Braz-Petta T, et al. (2011). The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol eta in response to oxidative DNA damage in human cells. Mol Cell 43: 649-62
306. Zu T, Liu Y, Banez-Coronel M, et al. (2013). RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proc Natl Acad Sci USA 110: E4968-77