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Molecular Mechanisms and Functions of DNA Mismatch Repair

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DNA Alterations in Lynch Syndrome

Abstract

DNA mismatch repair (MMR) is an evolutionarily conserved DNA repair pathway that plays an essential role in maintaining genomic fidelity and stability. MMR targets errors generated during DNA replication, contributing 100–1,000-fold to the overall fidelity of DNA replication. Inactivating mutations in highly conserved MMR genes greatly increase the spontaneous mutation rate, and loss of MMR predisposes individuals to hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome. Loss of MMR activity due to epigenetic silencing of MMR genes or somatic mutation is associated with a variety of sporadic tumors. Proteins involved in MMR also participate in DNA damage signaling inducing cell cycle arrest and apoptosis in response to certain DNA alkylating agents and other DNA-damaging agents or base analogs. This review summarizes our current understanding of the MMR pathway and its roles in cancer avoidance.

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References

  1. Harfe BD, Jinks-Robertson S (2000) DNA mismatch repair and genetic instability. Annu Rev Genet 34:359–399. doi:10.1146/annurev.genet.34.1.359, 34/1/359 [pii]

    CAS  PubMed  Google Scholar 

  2. Kunkel TA, Erie DA (2005) DNA mismatch repair. Annu Rev Biochem 74:681–710. doi:10.1146/annurev.biochem.74.082803.133243

    CAS  PubMed  Google Scholar 

  3. Jiricny J (2006) The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol 7(5):335–346. doi:10.1038/nrm1907, nrm1907 [pii]

    CAS  PubMed  Google Scholar 

  4. Hsieh P, Yamane K (2008) DNA mismatch repair: molecular mechanism, cancer, and ageing. Mech Ageing Dev 129(7–8):391–407

    CAS  PubMed  Google Scholar 

  5. Li GM (2008) Mechanisms and functions of DNA mismatch repair. Cell Res 18(1):85–98. doi:10.1038/cr.2007.115, cr2007115 [pii]

    CAS  PubMed  Google Scholar 

  6. Iyer RR, Pluciennik A, Burdett V, Modrich PL (2006) DNA mismatch repair: functions and mechanisms. Chem Rev 106(2):302–323. doi:10.1021/cr0404794

    CAS  PubMed  Google Scholar 

  7. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR (2009) Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet 76(1):1–18. doi:10.1111/j.1399-0004.2009.01230.x, CGE1230 [pii]

    CAS  PubMed  Google Scholar 

  8. Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337. doi:10.1038/nature11252, nature11252 [pii]

    Google Scholar 

  9. Ehmsen KT, Heyer WD (2008) Biochemistry of meiotic recombination: formation, processing, and resolution of recombination intermediates. Genome Dyn Stab 3:91. doi:10.1007/7050_2008_039

    PubMed  Google Scholar 

  10. Chahwan R, Edelmann W, Scharff MD, Roa S (2012) AIDing antibody diversity by error-­prone mismatch repair. Semin Immunol 24(4):293–300. doi:10.1016/j.smim.2012.05.005, S1044-5323(12)00066-8 [pii]

    CAS  PubMed  Google Scholar 

  11. Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR et al (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260(5109):812–816

    CAS  PubMed  Google Scholar 

  12. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363(6429):558–561. doi:10.1038/363558a0

    CAS  PubMed  Google Scholar 

  13. Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260(5109):816–819

    CAS  PubMed  Google Scholar 

  14. Soreide K (2007) Molecular testing for microsatellite instability and DNA mismatch repair defects in hereditary and sporadic colorectal cancers–ready for prime time? Tumour Biol 28(5):290–300

    PubMed  Google Scholar 

  15. Strand M, Prolla TA, Liskay RM, Petes TD (1993) Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365(6443):274–276. doi:10.1038/365274a0

    CAS  PubMed  Google Scholar 

  16. Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75(5):1027–1038

    CAS  PubMed  Google Scholar 

  17. Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M et al (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75(6):1215–1225

    CAS  PubMed  Google Scholar 

  18. Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD et al (1994) Mutation of a mutL homolog in hereditary colon cancer. Science 263(5153):1625–1629

    CAS  PubMed  Google Scholar 

  19. Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, Kane M, Earabino C, Lipford J, Lindblom A et al (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368(6468):258–261. doi:10.1038/368258a0

    CAS  PubMed  Google Scholar 

  20. Wu Y, Berends MJ, Mensink RG, Kempinga C, Sijmons RH, van Der Zee AG, Hollema H, Kleibeuker JH, Buys CH, Hofstra RM (1999) Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am J Hum Genet 65(5):1291–1298

    CAS  PubMed  Google Scholar 

  21. Wijnen J, de Leeuw W, Vasen H, van der Klift H, Moller P, Stormorken A, Meijers-Heijboer H, Lindhout D, Menko F, Vossen S, Moslein G, Tops C, Brocker-Vriends A, Wu Y, Hofstra R, Sijmons R, Cornelisse C, Morreau H, Fodde R (1999) Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat Genet 23(2):142–144. doi:10.1038/13773

    CAS  PubMed  Google Scholar 

  22. Woods MO, Williams P, Careen A, Edwards L, Bartlett S, McLaughlin JR, Younghusband HB (2007) A new variant database for mismatch repair genes associated with Lynch syndrome. Hum Mutat 28(7):669–673. doi:10.1002/humu.20502

    CAS  PubMed  Google Scholar 

  23. Ou J, Niessen RC, Vonk J, Westers H, Hofstra RM, Sijmons RH (2008) A database to support the interpretation of human mismatch repair gene variants. Hum Mutat 29(11):1337–1341. doi:10.1002/humu.20907

    CAS  PubMed  Google Scholar 

  24. Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P (1993) Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 75(6):1227–1236, 0092-8674(93)90331-J [pii]

    CAS  PubMed  Google Scholar 

  25. Umar A, Boyer JC, Thomas DC, Nguyen DC, Risinger JI, Boyd J, Ionov Y, Perucho M, Kunkel TA (1994) Defective mismatch repair in extracts of colorectal and endometrial cancer cell lines exhibiting microsatellite instability. J Biol Chem 269(20):14367–14370

    CAS  PubMed  Google Scholar 

  26. Drummond JT, Li GM, Longley MJ, Modrich P (1995) Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science 268(5219):1909–1912

    CAS  PubMed  Google Scholar 

  27. Li GM, Modrich P (1995) Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs. Proc Natl Acad Sci U S A 92(6):1950–1954

    CAS  PubMed  Google Scholar 

  28. Koi M, Umar A, Chauhan DP, Cherian SP, Carethers JM, Kunkel TA, Boland CR (1994) Human chromosome 3 corrects mismatch repair deficiency and microsatellite instability and reduces N-methyl-N′-nitro-N-nitrosoguanidine tolerance in colon tumor cells with homozygous hMLH1 mutation. Cancer Res 54(16):4308–4312

    CAS  PubMed  Google Scholar 

  29. Umar A, Koi M, Risinger JI, Glaab WE, Tindall KR, Kolodner RD, Boland CR, Barrett JC, Kunkel TA (1997) Correction of hypermutability, N-methyl-N′-nitro-N-nitrosoguanidine resistance, and defective DNA mismatch repair by introducing chromosome 2 into human tumor cells with mutations in MSH2 and MSH6. Cancer Res 57(18):3949–3955

    CAS  PubMed  Google Scholar 

  30. Risinger JI, Umar A, Glaab WE, Tindall KR, Kunkel TA, Barrett JC (1998) Single gene complementation of the hPMS2 defect in HEC-1-A endometrial carcinoma cells. Cancer Res 58(14):2978–2981

    CAS  PubMed  Google Scholar 

  31. Tindall KR, Glaab WE, Umar A, Risinger JI, Koi M, Barrett JC, Kunkel TA (1998) Complementation of mismatch repair gene defects by chromosome transfer. Mutat Res 402(1–2):15–22

    CAS  PubMed  Google Scholar 

  32. Warren JJ, Pohlhaus TJ, Changela A, Iyer RR, Modrich PL, Beese LS (2007) Structure of the human MutSalpha DNA lesion recognition complex. Mol Cell 26(4):579–592. doi:10.1016/j.molcel.2007.04.018, S1097-2765(07)00254-7 [pii]

    CAS  PubMed  Google Scholar 

  33. Liu B, Nicolaides NC, Markowitz S, Willson JK, Parsons RE, Jen J, Papadopolous N, Peltomaki P, de la Chapelle A, Hamilton SR et al (1995) Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet 9(1):48–55. ­doi:10.1038/ng0195-48

    CAS  PubMed  Google Scholar 

  34. Thibodeau SN, French AJ, Roche PC, Cunningham JM, Tester DJ, Lindor NM, Moslein G, Baker SM, Liskay RM, Burgart LJ, Honchel R, Halling KC (1996) Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes. Cancer Res 56(21):4836–4840

    CAS  PubMed  Google Scholar 

  35. Borresen AL, Lothe RA, Meling GI, Lystad S, Morrison P, Lipford J, Kane MF, Rognum TO, Kolodner RD (1995) Somatic mutations in the hMSH2 gene in microsatellite unstable colorectal carcinomas. Hum Mol Genet 4(11):2065–2072

    CAS  PubMed  Google Scholar 

  36. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM, Kolodner R (1997) Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57(5):808–811

    CAS  PubMed  Google Scholar 

  37. Jenkins MA, Hayashi S, O’Shea AM, Burgart LJ, Smyrk TC, Shimizu D, Waring PM, Ruszkiewicz AR, Pollett AF, Redston M, Barker MA, Baron JA, Casey GR, Dowty JG, Giles GG, Limburg P, Newcomb P, Young JP, Walsh MD, Thibodeau SN, Lindor NM, Lemarchand L, Gallinger S, Haile RW, Potter JD, Hopper JL, Jass JR (2007) Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology 133(1):48–56

    CAS  PubMed  Google Scholar 

  38. Samowitz WS, Curtin K, Lin HH, Robertson MA, Schaffer D, Nichols M, Gruenthal K, Leppert MF, Slattery ML (2001) The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer. Gastroenterology 121(4):830–838

    CAS  PubMed  Google Scholar 

  39. Veigl ML, Kasturi L, Olechnowicz J, Ma AH, Lutterbaugh JD, Periyasamy S, Li GM, Drummond J, Modrich PL, Sedwick WD, Markowitz SD (1998) Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci U S A 95(15):8698–8702

    CAS  PubMed  Google Scholar 

  40. Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA, Baylin SB (1998) Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 95(12):6870–6875

    CAS  PubMed  Google Scholar 

  41. Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ, Thibodeau SN (1998) Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58(15):3455–3460

    CAS  PubMed  Google Scholar 

  42. Mueller J, Gazzoli I, Bandipalliam P, Garber JE, Syngal S, Kolodner RD (2009) Comprehensive molecular analysis of mismatch repair gene defects in suspected Lynch syndrome (hereditary nonpolyposis colorectal cancer) cases. Cancer Res 69(17):7053–7061. doi:10.1158/0008-5472.CAN-09-0358, 0008–5472.CAN-09-0358 [pii]

    CAS  PubMed  Google Scholar 

  43. Edelmann L, Edelmann W (2004) Loss of DNA mismatch repair function and cancer predisposition in the mouse: animal models for human hereditary nonpolyposis colorectal cancer. Am J Med Genet C Semin Med Genet 129C(1):91–99. doi:10.1002/ajmg.c.30021

    PubMed  Google Scholar 

  44. Wei K, Kucherlapati R, Edelmann W (2002) Mouse models for human DNA mismatch-repair gene defects. Trends Mol Med 8(7):346–353

    CAS  PubMed  Google Scholar 

  45. de Wind N, Dekker M, Berns A, Radman M, te Riele H (1995) Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82(2):321–330

    PubMed  Google Scholar 

  46. Reitmair AH, Schmits R, Ewel A, Bapat B, Redston M, Mitri A, Waterhouse P, Mittrucker HW, Wakeham A, Liu B et al (1995) MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet 11(1):64–70

    CAS  PubMed  Google Scholar 

  47. de Wind N, Dekker M, van Rossum A, van der Valk M, te Riele H (1998) Mouse models for hereditary nonpolyposis colorectal cancer. Cancer Res 58(2):248–255

    PubMed  Google Scholar 

  48. Edelmann W, Yang K, Umar A, Heyer J, Lau K, Fan K, Liedtke W, Cohen PE, Kane MF, Lipford JR, Yu N, Crouse GF, Pollard JW, Kunkel T, Lipkin M, Kolodner R, Kucherlapati R (1997) Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell 91(4):467–477, S0092-8674(00)80433-X [pii]

    CAS  PubMed  Google Scholar 

  49. de Wind N, Dekker M, Claij N, Jansen L, van Klink Y, Radman M, Riggins G, van der Valk M, van’t Wout K, te Riele H (1999) HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. Nat Genet 23(3):359–362

    PubMed  Google Scholar 

  50. Edelmann W, Umar A, Yang K, Heyer J, Kucherlapati M, Lia M, Kneitz B, Avdievich E, Fan K, Wong E, Crouse G, Kunkel T, Lipkin M, Kolodner RD, Kucherlapati R (2000) The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Res 60(4):803–807

    CAS  PubMed  Google Scholar 

  51. Baker SM, Plug AW, Prolla TA, Bronner CE, Harris AC, Yao X, Christie DM, Monell C, Arnheim N, Bradley A, Ashley T, Liskay RM (1996) Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet 13(3):336–342. doi:10.1038/ng0796-336

    CAS  PubMed  Google Scholar 

  52. Edelmann W, Cohen PE, Kane M, Lau K, Morrow B, Bennett S, Umar A, Kunkel T, Cattoretti G, Chaganti R, Pollard JW, Kolodner RD, Kucherlapati R (1996) Meiotic pachytene arrest in MLH1-deficient mice. Cell 85(7):1125–1134

    CAS  PubMed  Google Scholar 

  53. Baker SM, Bronner CE, Zhang L, Plug AW, Robatzek M, Warren G, Elliott EA, Yu J, Ashley T, Arnheim N, Flavell RA, Liskay RM (1995) Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82(2):309–319, 0092-8674(95)90318-6 [pii]

    CAS  PubMed  Google Scholar 

  54. Wei K, Clark AB, Wong E, Kane MF, Mazur DJ, Parris T, Kolas NK, Russell R, Hou H Jr, Kneitz B, Yang G, Kunkel TA, Kolodner RD, Cohen PE, Edelmann W (2003) Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility. Genes Dev 17(5):603–614

    CAS  PubMed  Google Scholar 

  55. Lin DP, Wang Y, Scherer SJ, Clark AB, Yang K, Avdievich E, Jin B, Werling U, Parris T, Kurihara N, Umar A, Kucherlapati R, Lipkin M, Kunkel TA, Edelmann W (2004) An Msh2 point mutation uncouples DNA mismatch repair and apoptosis. Cancer Res 64(2):517–522

    CAS  PubMed  Google Scholar 

  56. Yang G, Scherer SJ, Shell SS, Yang K, Kim M, Lipkin M, Kucherlapati R, Kolodner RD, Edelmann W (2004) Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell 6(2):139–150. doi:10.1016/j.ccr.2004.06.024, S1535610804002089 [pii]

    CAS  PubMed  Google Scholar 

  57. Avdievich E, Reiss C, Scherer SJ, Zhang Y, Maier SM, Jin B, Hou H Jr, Rosenwald A, Riedmiller H, Kucherlapati R, Cohen PE, Edelmann W, Kneitz B (2008) Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis. Proc Natl Acad Sci U S A 105(11):4247–4252. doi:10.1073/pnas.0800276105, 0800276105 [pii]

    CAS  PubMed  Google Scholar 

  58. van Oers JM, Roa S, Werling U, Liu Y, Genschel J, Hou H Jr, Sellers RS, Modrich P, Scharff MD, Edelmann W (2010) PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. Proc Natl Acad Sci U S A 107(30):13384–13389. doi:10.1073/pnas.1008589107, 1008589107 [pii]

    PubMed  Google Scholar 

  59. Matson SW, Robertson AB (2006) The UvrD helicase and its modulation by the mismatch repair protein MutL. Nucleic Acids Res 34(15):4089–4097. doi:10.1093/nar/gkl450, gkl450 [pii]

    CAS  PubMed  Google Scholar 

  60. Robertson AB, Pattishall SR, Gibbons EA, Matson SW (2006) MutL-catalyzed ATP hydrolysis is required at a post-UvrD loading step in methyl-directed mismatch repair. J Biol Chem 281(29):19949–19959. doi:10.1074/jbc.M601604200, M601604200 [pii]

    CAS  PubMed  Google Scholar 

  61. Burdett V, Baitinger C, Viswanathan M, Lovett ST, Modrich P (2001) In vivo requirement for RecJ, ExoVII, ExoI, and ExoX in methyl-directed mismatch repair. Proc Natl Acad Sci U S A 98(12):6765–6770. doi:10.1073/pnas.121183298, 121183298 [pii]

    CAS  PubMed  Google Scholar 

  62. Modrich P (2006) Mechanisms in eukaryotic mismatch repair. J Biol Chem 281(41):30305–30309. doi:10.1074/jbc.R600022200, R600022200 [pii]

    CAS  PubMed  Google Scholar 

  63. Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, Kolodner R, Fishel R (1996) hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci U S A 93(24):13629–13634

    CAS  PubMed  Google Scholar 

  64. Marsischky GT, Kolodner RD (1999) Biochemical characterization of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 complex and mispaired bases in DNA. J Biol Chem 274(38):26668–26682

    CAS  PubMed  Google Scholar 

  65. Constantin N, Dzantiev L, Kadyrov FA, Modrich P (2005) Human mismatch repair: reconstitution of a nick-directed bidirectional reaction. J Biol Chem 280(48):39752–39761. doi:10.1074/jbc.M509701200, M509701200 [pii]

    CAS  PubMed  Google Scholar 

  66. Dzantiev L, Constantin N, Genschel J, Iyer RR, Burgers PM, Modrich P (2004) A defined human system that supports bidirectional mismatch-provoked excision. Mol Cell 15(1):31–41. doi:10.1016/j.molcel.2004.06.016, S1097276504003442 [pii]

    CAS  PubMed  Google Scholar 

  67. Zhang Y, Yuan F, Presnell SR, Tian K, Gao Y, Tomkinson AE, Gu L, Li GM (2005) Reconstitution of 5′-directed human mismatch repair in a purified system. Cell 122(5):693–705

    CAS  PubMed  Google Scholar 

  68. Yuan F, Gu L, Guo S, Wang C, Li GM (2004) Evidence for involvement of HMGB1 protein in human DNA mismatch repair. J Biol Chem 279(20):20935–20940. doi:10.1074/jbc.M401931200, M401931200 [pii]

    CAS  PubMed  Google Scholar 

  69. Warren JJ, Forsberg LJ, Beese LS (2006) The structural basis for the mutagenicity of O(6)-methyl-guanine lesions. Proc Natl Acad Sci U S A 103(52):19701–19706. doi:10.1073/pnas.0609580103, 0609580103 [pii]

    CAS  PubMed  Google Scholar 

  70. Gupta S, Gellert M, Yang W (2012) Mechanism of mismatch recognition revealed by human MutSbeta bound to unpaired DNA loops. Nat Struct Mol Biol 19(1):72–78. doi:10.1038/nsmb.2175, nsmb.2175 [pii]

    CAS  Google Scholar 

  71. Obmolova G, Ban C, Hsieh P, Yang W (2000) Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA. Nature 407(6805):703–710. doi:10.1038/35037509

    CAS  PubMed  Google Scholar 

  72. Lamers MH, Perrakis A, Enzlin JH, Winterwerp HH, de Wind N, Sixma TK (2000) The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch. Nature 407(6805):711–717. doi:10.1038/35037523

    CAS  PubMed  Google Scholar 

  73. Tian L, Gu L, Li GM (2009) Distinct nucleotide binding/hydrolysis properties and molar ratio of MutSalpha and MutSbeta determine their differential mismatch binding activities. J Biol Chem 284(17):11557–11562. doi:10.1074/jbc.M900908200, M900908200 [pii]

    CAS  PubMed  Google Scholar 

  74. Owen BA, Lang WH, McMurray CT (2009) The nucleotide binding dynamics of human MSH2-MSH3 are lesion dependent. Nat Struct Mol Biol 16(5):550–557. doi:10.1038/nsmb.1596, nsmb.1596 [pii]

    CAS  PubMed  Google Scholar 

  75. Antony E, Hingorani MM (2003) Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP-bound state at the initiation of DNA repair. Biochemistry 42(25):7682–7693. doi:10.1021/bi034602h

    CAS  PubMed  Google Scholar 

  76. Antony E, Khubchandani S, Chen S, Hingorani MM (2006) Contribution of Msh2 and Msh6 subunits to the asymmetric ATPase and DNA mismatch binding activities of Saccharomyces cerevisiae Msh2-Msh6 mismatch repair protein. DNA Repair (Amst) 5(2):153–162. doi:10.1016/j.dnarep.2005.08.016, S1568-7864(05)00221-1 [pii]

    CAS  Google Scholar 

  77. Martik D, Baitinger C, Modrich P (2004) Differential specificities and simultaneous occupancy of human MutSalpha nucleotide binding sites. J Biol Chem 279(27):28402–28410. doi:10.1074/jbc.M312108200, M312108200 [pii]

    CAS  PubMed  Google Scholar 

  78. Gradia S, Subramanian D, Wilson T, Acharya S, Makhov A, Griffith J, Fishel R (1999) hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA. Mol Cell 3(2):255–261, S1097-2765(00)80316-0 [pii]

    CAS  PubMed  Google Scholar 

  79. Mendillo ML, Mazur DJ, Kolodner RD (2005) Analysis of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 and MLH1-PMS1 complexes with DNA using a reversible DNA end-blocking system. J Biol Chem 280(23):22245–22257. doi:10.1074/jbc.M407545200, M407545200 [pii]

    CAS  PubMed  Google Scholar 

  80. Gorman J, Chowdhury A, Surtees JA, Shimada J, Reichman DR, Alani E, Greene EC (2007) Dynamic basis for one-dimensional DNA scanning by the mismatch repair complex Msh2-­Msh6. Mol Cell 28(3):359–370. doi:10.1016/j.molcel.2007.09.008, S1097-2765(07)00618-1 [pii]

    CAS  PubMed  Google Scholar 

  81. Zhai J, Hingorani MM (2010) Saccharomyces cerevisiae Msh2-Msh6 DNA binding kinetics reveal a mechanism of targeting sites for DNA mismatch repair. Proc Natl Acad Sci U S A 107(2):680–685. doi:10.1073/pnas.0908302107, 0908302107 [pii]

    CAS  PubMed  Google Scholar 

  82. Blackwell LJ, Martik D, Bjornson KP, Bjornson ES, Modrich P (1998) Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism. J Biol Chem 273(48):32055–32062

    CAS  PubMed  Google Scholar 

  83. Hargreaves VV, Shell SS, Mazur DJ, Hess MT, Kolodner RD (2010) Interaction between the Msh2 and Msh6 nucleotide-binding sites in the Saccharomyces cerevisiae Msh2-Msh6 complex. J Biol Chem 285(12):9301–9310. doi:10.1074/jbc.M109.096388, M109.096388 [pii]

    CAS  PubMed  Google Scholar 

  84. Heinen CD, Cyr JL, Cook C, Punja N, Sakato M, Forties RA, Lopez JM, Hingorani MM, Fishel R (2011) Human MSH2 (hMSH2) protein controls ATP processing by hMSH2-­hMSH6. J Biol Chem 286(46):40287–40295. doi:10.1074/jbc.M111.297523, M111.297523 [pii]

    CAS  PubMed  Google Scholar 

  85. Qiu R, DeRocco VC, Harris C, Sharma A, Hingorani MM, Erie DA, Weninger KR (2012) Large conformational changes in MutS during DNA scanning, mismatch recognition and repair signalling. EMBO J 31(11):2528–2540. doi:10.1038/emboj.2012.95, emboj201295 [pii]

    CAS  PubMed  Google Scholar 

  86. Hargreaves VV, Putnam CD, Kolodner RD (2012) Engineered disulfide-forming amino acid substitutions interfere with a conformational change in the mismatch recognition complex Msh2-Msh6 required for mismatch repair. J Biol Chem 287:41232–41244. doi:10.1074/jbc.M112.402495, M112.402495 [pii]

    CAS  PubMed  Google Scholar 

  87. Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM et al (1994) Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371(6492):75–80. doi:10.1038/371075a0

    CAS  PubMed  Google Scholar 

  88. Lipkin SM, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis AD, Lynch HT, Elliott RM, Collins FS (2000) MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet 24(1):27–35. doi:10.1038/71643

    CAS  PubMed  Google Scholar 

  89. Guarne A, Junop MS, Yang W (2001) Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase. EMBO J 20(19):5521–5531. doi:10.1093/emboj/20.19.5521

    CAS  PubMed  Google Scholar 

  90. Raschle M, Dufner P, Marra G, Jiricny J (2002) Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSalpha. J Biol Chem 277(24):21810–21820. doi:10.1074/jbc.M108787200, M108787200 [pii]

    CAS  PubMed  Google Scholar 

  91. Hall MC, Shcherbakova PV, Kunkel TA (2002) Differential ATP binding and intrinsic ATP hydrolysis by amino-terminal domains of the yeast Mlh1 and Pms1 proteins. J Biol Chem 277(5):3673–3679. doi:10.1074/jbc.M106120200, M106120200 [pii]

    CAS  PubMed  Google Scholar 

  92. Kadyrov FA, Dzantiev L, Constantin N, Modrich P (2006) Endonucleolytic function of MutLalpha in human mismatch repair. Cell 126(2):297–308. doi:10.1016/j.cell.2006.05.039, S0092-8674(06)00812-9 [pii]

    CAS  PubMed  Google Scholar 

  93. Kadyrov FA, Holmes SF, Arana ME, Lukianova OA, O’Donnell M, Kunkel TA, Modrich P (2007) Saccharomyces cerevisiae MutLalpha is a mismatch repair endonuclease. J Biol Chem 282(51):37181–37190. doi:10.1074/jbc.M707617200, M707617200 [pii]

    CAS  PubMed  Google Scholar 

  94. Pillon MC, Lorenowicz JJ, Uckelmann M, Klocko AD, Mitchell RR, Chung YS, Modrich P, Walker GC, Simmons LA, Friedhoff P, Guarne A (2010) Structure of the endonuclease domain of MutL: unlicensed to cut. Mol Cell 39(1):145–151. doi:10.1016/j.molcel.2010.06.027, S1097-2765(10)00494-6 [pii]

    CAS  PubMed  Google Scholar 

  95. Pluciennik A, Dzantiev L, Iyer RR, Constantin N, Kadyrov FA, Modrich P (2010) PCNA function in the activation and strand direction of MutLalpha endonuclease in mismatch repair. Proc Natl Acad Sci U S A 107(37):16066–16071. doi:10.1073/pnas.1010662107, 1010662107 [pii]

    CAS  PubMed  Google Scholar 

  96. Hombauer H, Campbell CS, Smith CE, Desai A, Kolodner RD (2011) Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair intermediates. Cell 147(5):1040–1053. doi:10.1016/j.cell.2011.10.025, S0092-8674(11)01275-X [pii]

    CAS  PubMed  Google Scholar 

  97. Smith BT, Grossman AD, Walker GC (2001) Visualization of mismatch repair in bacterial cells. Mol Cell 8(6):1197–1206, S1097-2765(01)00402-6 [pii]

    CAS  PubMed  Google Scholar 

  98. Genschel J, Bazemore LR, Modrich P (2002) Human exonuclease I is required for 5′ and 3′ mismatch repair. J Biol Chem 277(15):13302–13311. doi:10.1074/jbc.M111854200, M111854200 [pii]

    CAS  PubMed  Google Scholar 

  99. Schmutte C, Marinescu RC, Sadoff MM, Guerrette S, Overhauser J, Fishel R (1998) Human exonuclease I interacts with the mismatch repair protein hMSH2. Cancer Res 58(20):4537–4542

    CAS  PubMed  Google Scholar 

  100. Schmutte C, Sadoff MM, Shim KS, Acharya S, Fishel R (2001) The interaction of DNA mismatch repair proteins with human exonuclease I. J Biol Chem 276(35):33011–33018. doi:10.1074/jbc.M102670200, M102670200 [pii]

    CAS  PubMed  Google Scholar 

  101. Nielsen FC, Jager AC, Lutzen A, Bundgaard JR, Rasmussen LJ (2004) Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA. Oncogene 23(7):1457–1468. doi:10.1038/sj.onc.1207265, 1207265 [pii]

    CAS  PubMed  Google Scholar 

  102. Orans J, McSweeney EA, Iyer RR, Hast MA, Hellinga HW, Modrich P, Beese LS (2011) Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family. Cell 145(2):212–223. doi:10.1016/j.cell.2011.03.005, S0092-8674(11)00242-X [pii]

    CAS  PubMed  Google Scholar 

  103. Tsurimoto T (1999) PCNA binding proteins. Front Biosci 4:D849–D858

    CAS  PubMed  Google Scholar 

  104. Umar A, Buermeyer AB, Simon JA, Thomas DC, Clark AB, Liskay RM, Kunkel TA (1996) Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell 87(1):65–73, S0092-8674(00)81323-9 [pii]

    CAS  PubMed  Google Scholar 

  105. Gu L, Hong Y, McCulloch S, Watanabe H, Li GM (1998) ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair. Nucleic Acids Res 26(5):1173–1178, gkb225 [pii]

    CAS  PubMed  Google Scholar 

  106. Lau PJ, Kolodner RD (2003) Transfer of the MSH2.MSH6 complex from proliferating cell nuclear antigen to mispaired bases in DNA. J Biol Chem 278(1):14–17. doi:10.1074/jbc.C200627200, C200627200 [pii]

    CAS  PubMed  Google Scholar 

  107. Shell SS, Putnam CD, Kolodner RD (2007) The N terminus of Saccharomyces cerevisiae Msh6 is an unstructured tether to PCNA. Mol Cell 26(4):565–578. doi:10.1016/j.molcel.2007.04.024, S1097-2765(07)00262-6 [pii]

    CAS  PubMed  Google Scholar 

  108. Ramilo C, Gu L, Guo S, Zhang X, Patrick SM, Turchi JJ, Li GM (2002) Partial reconstitution of human DNA mismatch repair in vitro: characterization of the role of human replication protein A. Mol Cell Biol 22(7):2037–2046

    CAS  PubMed  Google Scholar 

  109. Guo S, Zhang Y, Yuan F, Gao Y, Gu L, Wong I, Li GM (2006) Regulation of replication protein A functions in DNA mismatch repair by phosphorylation. J Biol Chem 281(31):21607–21616. doi:10.1074/jbc.M603504200, M603504200 [pii]

    CAS  PubMed  Google Scholar 

  110. Lujan SA, Williams JS, Pursell ZF, Abdulovic-Cui AA, Clark AB, Nick McElhinny SA, Kunkel TA (2012) Mismatch repair balances leading and lagging strand DNA replication fidelity. PLoS Genet 8(10):e1003016. doi:10.1371/journal.pgen.1003016P, GENETICS-D-12-00710 [pii]

    CAS  PubMed  Google Scholar 

  111. Pena-Diaz J, Bregenhorn S, Ghodgaonkar M, Follonier C, Artola-Boran M, Castor D, Lopes M, Sartori AA, Jiricny J (2012) Noncanonical mismatch repair as a source of genomic instability in human cells. Mol Cell 47(5):669–680. doi:10.1016/j.molcel.2012.07.006, S1097-­2765(12)00601-6 [pii]

    CAS  PubMed  Google Scholar 

  112. Li LS, Morales JC, Veigl M, Sedwick D, Greer S, Meyers M, Wagner M, Fishel R, Boothman DA (2009) DNA mismatch repair (MMR)-dependent 5-fluorouracil cytotoxicity and the potential for new therapeutic targets. Br J Pharmacol 158(3):679–692. doi:10.1111/j.1476-5381.2009.00423.x, BPH423 [pii]

    CAS  PubMed  Google Scholar 

  113. Berardini M, Mazurek A, Fishel R (2000) The effect of O6-methylguanine DNA adducts on the adenosine nucleotide switch functions of hMSH2-hMSH6 and hMSH2-hMSH3. J Biol Chem 275(36):27851–27857. doi:10.1074/jbc.M003589200, M003589200 [pii]

    CAS  PubMed  Google Scholar 

  114. Duckett DR, Drummond JT, Murchie AI, Reardon JT, Sancar A, Lilley DM, Modrich P (1996) Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct. Proc Natl Acad Sci U S A 93(13):6443–6447

    CAS  PubMed  Google Scholar 

  115. Yoshioka K, Yoshioka Y, Hsieh P (2006) ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell 22(4):501–510

    CAS  PubMed  Google Scholar 

  116. Karran P (2001) Mechanisms of tolerance to DNA damaging therapeutic drugs. Carcinogenesis 22(12):1931–1937

    CAS  PubMed  Google Scholar 

  117. Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL, Baskaran R (2003) The mismatch repair system is required for S-phase checkpoint activation. Nat Genet 33(1):80–84. doi:10.1038/ng1052, ng1052 [pii]

    CAS  PubMed  Google Scholar 

  118. Kim WJ, Rajasekaran B, Brown KD (2007) MLH1- and ATM-dependent MAPK signaling is activated through c-Abl in response to the alkylator N-methyl-N′-nitro-N′-nitrosoguanidine. J Biol Chem 282(44):32021–32031. doi:10.1074/jbc.M701451200, M701451200 [pii]

    CAS  PubMed  Google Scholar 

  119. Shimodaira H, Yoshioka-Yamashita A, Kolodner RD, Wang JY (2003) Interaction of mismatch repair protein PMS2 and the p53-related transcription factor p73 in apoptosis response to cisplatin. Proc Natl Acad Sci U S A 100(5):2420–2425. doi:10.1073/pnas.0438031100, 0438031100 [pii]

    CAS  PubMed  Google Scholar 

  120. Liu Y, Fang Y, Shao H, Lindsey-Boltz L, Sancar A, Modrich P (2010) Interactions of human mismatch repair proteins MutSalpha and MutLalpha with proteins of the ATR-Chk1 pathway. J Biol Chem 285(8):5974–5982. doi:10.1074/jbc.M109.076109, M109.076109 [pii]

    CAS  PubMed  Google Scholar 

  121. York SJ, Modrich P (2006) Mismatch repair-dependent iterative excision at irreparable O6-methylguanine lesions in human nuclear extracts. J Biol Chem 281(32):22674–22683. doi:10.1074/jbc.M603667200, M603667200 [pii]

    CAS  PubMed  Google Scholar 

  122. Tominaga Y, Tsuzuki T, Shiraishi A, Kawate H, Sekiguchi M (1997) Alkylation-induced apoptosis of embryonic stem cells in which the gene for DNA-repair, methyltransferase, had been disrupted by gene targeting. Carcinogenesis 18(5):889–896

    CAS  PubMed  Google Scholar 

  123. Stojic L, Mojas N, Cejka P, Di Pietro M, Ferrari S, Marra G, Jiricny J (2004) Mismatch repair-dependent G2 checkpoint induced by low doses of SN1 type methylating agents requires the ATR kinase. Genes Dev 18(11):1331–1344. doi:10.1101/gad.29440418/11/1331 [pii]

    CAS  PubMed  Google Scholar 

  124. Goldmacher VS, Cuzick RA Jr, Thilly WG (1986) Isolation and partial characterization of human cell mutants differing in sensitivity to killing and mutation by methylnitrosourea and N-methyl-N′-nitro-N-nitrosoguanidine. J Biol Chem 261(27):12462–12471

    CAS  PubMed  Google Scholar 

  125. Karran P, Bignami M (1992) Self-destruction and tolerance in resistance of mammalian cells to alkylation damage. Nucleic Acids Res 20(12):2933–2940

    CAS  PubMed  Google Scholar 

  126. Mojas N, Lopes M, Jiricny J (2007) Mismatch repair-dependent processing of methylation damage gives rise to persistent single-stranded gaps in newly replicated DNA. Genes Dev 21(24):3342–3355. doi:10.1101/gad.455407, 21/24/3342 [pii]

    CAS  PubMed  Google Scholar 

  127. Kat A, Thilly WG, Fang WH, Longley MJ, Li GM, Modrich P (1993) An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. Proc Natl Acad Sci U S A 90(14):6424–6428

    CAS  PubMed  Google Scholar 

  128. Li GM (1999) The role of mismatch repair in DNA damage-induced apoptosis. Oncol Res 11(9):393–400

    CAS  PubMed  Google Scholar 

  129. Fishel R (1999) Signaling mismatch repair in cancer. Nat Med 5(11):1239–1241. doi:10.1038/15191

    CAS  PubMed  Google Scholar 

  130. Pabla N, Ma Z, McIlhatton MA, Fishel R, Dong Z (2011) hMSH2 recruits ATR to DNA damage sites for activation during DNA damage-induced apoptosis. J Biol Chem 286(12):10411–10418. doi:10.1074/jbc.M110.210989, M110.210989 [pii]

    CAS  PubMed  Google Scholar 

  131. Martin-Lopez JV, Barrios Y, Medina-Arana V, Andujar M, Lee S, Gu L, Li GM, Ruschoff J, Salido E, Fishel R (2012) The hMSH2(M688R) Lynch syndrome mutation may function as a dominant negative. Carcinogenesis 33(9):1647–1654. doi:10.1093/carcin/bgs199, bgs199 [pii]

    CAS  PubMed  Google Scholar 

  132. Geng H, Sakato M, DeRocco V, Yamane K, Du C, Erie DA, Hingorani M, Hsieh P (2012) Biochemical analysis of the human mismatch repair proteins hMutSalpha MSH2(G674A)-MSH6 and MSH2-MSH6(T1219D). J Biol Chem 287(13):9777–9791. doi:10.1074/jbc.M111.316919, M111.316919 [pii]

    CAS  PubMed  Google Scholar 

  133. Gorman J, Plys AJ, Visnapuu ML, Alani E, Greene EC (2010) Visualizing one-dimensional diffusion of eukaryotic DNA repair factors along a chromatin lattice. Nat Struct Mol Biol 17(8):932–938. doi:10.1038/nsmb.1858, nsmb.1858 [pii]

    CAS  PubMed  Google Scholar 

  134. Li F, Tian L, Gu L, Li GM (2009) Evidence that nucleosomes inhibit mismatch repair in eukaryotic cells. J Biol Chem 284(48):33056–33061. doi:10.1074/jbc.M109.049874, M109.049874 [pii]

    CAS  PubMed  Google Scholar 

  135. Javaid S, Manohar M, Punja N, Mooney A, Ottesen JJ, Poirier MG, Fishel R (2009) Nucleosome remodeling by hMSH2-hMSH6. Mol Cell 36(6):1086–1094. doi:10.1016/j.molcel.2009.12.010, S1097-2765(09)00914-9 [pii]

    CAS  PubMed  Google Scholar 

  136. Schopf B, Bregenhorn S, Quivy JP, Kadyrov FA, Almouzni G, Jiricny J (2012) Interplay between mismatch repair and chromatin assembly. Proc Natl Acad Sci U S A 109(6):1895–1900. doi:10.1073/pnas.1106696109, 1106696109 [pii]

    CAS  PubMed  Google Scholar 

  137. Valeri N, Gasparini P, Braconi C, Paone A, Lovat F, Fabbri M, Sumani KM, Alder H, Amadori D, Patel T, Nuovo GJ, Fishel R, Croce CM (2010) MicroRNA-21 induces resistance to 5-­fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2). Proc Natl Acad Sci U S A 107(49):21098–21103. doi:10.1073/pnas.1015541107, 1015541107 [pii]

    CAS  PubMed  Google Scholar 

  138. Zhong Z, Dong Z, Yang L, Gong Z (2012) miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer. J Cancer Res Clin Oncol 138(10):1781–1788. doi:10.1007/s00432-012-1287-y

    CAS  PubMed  Google Scholar 

  139. Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard ML, Dunlop MG, Ho JW, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJ, Vasen HF, Barker G, Crawford G, Elliott F, Movahedi M, Pylvanainen K, Wijnen JT, Fodde R, Lynch HT, Mathers JC, Bishop DT (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378(9809):2081–2087. doi:10.1016/S0140-6736(11)61049-0, S0140-6736(11)61049-0 [pii]

    PubMed  Google Scholar 

  140. Ruschoff J, Wallinger S, Dietmaier W, Bocker T, Brockhoff G, Hofstadter F, Fishel R (1998) Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection. Proc Natl Acad Sci U S A 95(19):11301–11306

    CAS  PubMed  Google Scholar 

  141. McIlhatton MA, Tyler J, Kerepesi LA, Bocker-Edmonston T, Kucherlapati MH, Edelmann W, Kucherlapati R, Kopelovich L, Fishel R (2011) Aspirin and low-dose nitric oxide-­donating aspirin increase life span in a Lynch syndrome mouse model. Cancer Prev Res (Phila) 4(5):684–693. doi:10.1158/1940-6207.CAPR-10-0319, 1940–6207.CAPR-10-0319 [pii]

    CAS  Google Scholar 

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  1. Genetic and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA

    Hui Geng & Peggy Hsieh

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    Matjaž Vogelsang

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Geng, H., Hsieh, P. (2013). Molecular Mechanisms and Functions of DNA Mismatch Repair. In: Vogelsang, M. (eds) DNA Alterations in Lynch Syndrome. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6597-9_2

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