title: DNA mismatch repair and oxidative DNA damage: implications for cancer biology and treatment.
abstract: Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. g.bridge@qmul.ac.uk.
authors.forename: Gemma
authors.initials: G
authors.lastname: Bridge
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. sukaina.rashid@qmul.ac.uk.
authors.forename: Sukaina
authors.initials: S
authors.lastname: Rashid
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. sarah.martin@qmul.ac.uk.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Martin
references.citation: Mol Cell. 2011 Aug 19;43(4):649-62
references.pmid: 21855803
references.citation: Cancer Res. 2005 Dec 1;65(23):10759-66
references.pmid: 16322221
references.citation: Clin Cancer Res. 2010 Nov 1;16(21):5107-13
references.pmid: 20823149
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11915-20
references.pmid: 9751765
references.citation: Cell. 2003 Nov 26;115(5):629-40
references.pmid: 14651853
references.citation: Oncogene. 1998 Oct 15;17(15):1931-7
references.pmid: 9788436
references.citation: Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9463-8
references.pmid: 9256505
references.citation: J Biol Chem. 2002 Mar 8;277(10):8260-6
references.pmid: 11756455
references.citation: J Biol Chem. 2002 Mar 29;277(13):11135-42
references.pmid: 11801590
references.citation: Cancer Lett. 2012 Dec 31;327(1-2):26-47
references.pmid: 22293091
references.citation: Nature. 2007 Mar 8;446(7132):153-8
references.pmid: 17344846
references.citation: Nat Genet. 2013 Sep;45(9):970-6
references.pmid: 23852170
references.citation: Genetics. 1992 Dec;132(4):975-85
references.pmid: 1334021
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3832-7
references.pmid: 10759556
references.citation: DNA Repair (Amst). 2007 Mar 1;6(3):355-66
references.pmid: 17188944
references.citation: J Biol Chem. 1998 Jul 31;273(31):19895-901
references.pmid: 9677427
references.citation: Antioxid Redox Signal. 2013 Jun 20;18(18):2420-8
references.pmid: 23121537
references.citation: Antioxid Redox Signal. 2011 Jun 15;14(12):2491-507
references.pmid: 20649466
references.citation: J Clin Oncol. 2005 Jan 20;23(3):609-18
references.pmid: 15659508
references.citation: Mol Microbiol. 2005 Oct;58(1):166-76
references.pmid: 16164556
references.citation: Fam Cancer. 2008;7(1):27-39
references.pmid: 17999161
references.citation: Nat Rev Drug Discov. 2013 Dec;12(12):931-47
references.pmid: 24287781
references.citation: Curr Biol. 2002 Jun 4;12(11):912-8
references.pmid: 12062055
references.citation: Gynecol Oncol. 2014 May;133(2):362-9
references.pmid: 24607283
references.citation: J Biol Chem. 1993 Nov 5;268(31):23524-30
references.pmid: 8226881
references.citation: J Physiol Pharmacol. 2006 Sep;57 Suppl 3:51-65
references.pmid: 17033105
references.citation: Nucleic Acids Res. 2005 Sep 20;33(16):5094-105
references.pmid: 16174844
references.citation: Annu Rev Biochem. 2005;74:681-710
references.pmid: 15952900
references.citation: Mutat Res. 2009 Mar 31;674(1-2):123-30
references.pmid: 18955159
references.citation: DNA Repair (Amst). 2009 Jun 4;8(6):704-19
references.pmid: 19272840
references.citation: Mol Cell. 1999 Sep;4(3):439-44
references.pmid: 10518225
references.citation: Curr Opin Genet Dev. 1999 Feb;9(1):89-96
references.pmid: 10072354
references.citation: Integr Cancer Ther. 2004 Dec;3(4):294-300
references.pmid: 15523100
references.citation: Biochemistry. 1989 Oct 3;28(20):7979-84
references.pmid: 2690930
references.citation: Int J Oncol. 2000 Jan;16(1):133-9
references.pmid: 10601558
references.citation: Gynecol Oncol. 2014 Feb;132(2):506-12
references.pmid: 24333356
references.citation: Trends Genet. 2012 Nov;28(11):566-73
references.pmid: 22824526
references.citation: Curr Mol Pharmacol. 2012 Jan;5(1):88-101
references.pmid: 22122466
references.citation: Carcinogenesis. 2001 Oct;22(10):1709-13
references.pmid: 11577013
references.citation: Cell Death Dis. 2013 Oct 31;4:e891
references.pmid: 24176849
references.citation: Cell Biochem Biophys. 2001;35(2):141-70
references.pmid: 11892789
references.citation: Int Rev Immunol. 2013 Jun;32(3):249-70
references.pmid: 23617726
references.citation: Br J Cancer. 2013 Mar 5;108(4):983-92
references.pmid: 23361057
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6319-23
references.pmid: 8022779
references.citation: Gynecol Oncol. 2010 May;117(2):234-8
references.pmid: 20153885
references.citation: Carcinogenesis. 2003 Mar;24(3):353-62
references.pmid: 12663492
references.citation: Nat Rev Clin Oncol. 2010 Apr;7(4):197-208
references.pmid: 20177404
references.citation: Cell. 1993 Dec 17;75(6):1227-36
references.pmid: 8261516
references.citation: Cancer Res. 2009 May 15;69(10):4372-9
references.pmid: 19435918
references.citation: Mol Pharm. 2014 Apr 7;11(4):1282-93
references.pmid: 24555485
references.citation: Mutat Res. 2007 Jan 3;614(1-2):69-76
references.pmid: 16769088
references.citation: Cell Res. 2008 Jan;18(1):85-98
references.pmid: 18157157
references.citation: Proc Natl Acad Sci U S A. 2014 May 20;111(20):E2100-9
references.pmid: 24803433
references.citation: Int J Gynecol Pathol. 2009 May;28(3):239-55
references.pmid: 19620942
references.citation: Mutat Res. 2003 Oct 29;531(1-2):177-90
references.pmid: 14637254
references.citation: Nucleic Acids Res. 2002 Feb 1;30(3):711-8
references.pmid: 11809883
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1950-4
references.pmid: 7892206
references.citation: Rejuvenation Res. 2014 Jun;17(3):306-11
references.pmid: 24828241
references.citation: Int J Biol Sci. 2013 Dec 19;10(1):73-9
references.pmid: 24391453
references.citation: Cancer Res. 2012 Jun 15;72(12):3038-47
references.pmid: 22532167
references.citation: Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a001008
references.pmid: 20182602
references.citation: J Biol Chem. 2000 Jul 21;275(29):22355-62
references.pmid: 10801836
references.citation: Cancer Res. 2001 Feb 15;61(4):1392-7
references.pmid: 11245440
references.citation: Mutat Res. 2011 Jun 3;711(1-2):123-33
references.pmid: 21185841
references.citation: Nat Rev Mol Cell Biol. 2006 May;7(5):335-46
references.pmid: 16612326
references.citation: Biochem Pharmacol. 2012 May 1;83(9):1159-71
references.pmid: 22285910
references.citation: Mitochondrion. 2004 Jul;4(2-3):215-22
references.pmid: 16120387
references.citation: Curr Mol Pharmacol. 2012 Jan;5(1):3-13
references.pmid: 22122461
references.citation: Mutat Res. 2011 Jun 3;711(1-2):193-201
references.pmid: 21216256
references.citation: EMBO Mol Med. 2009 Sep;1(6-7):323-37
references.pmid: 20049736
references.citation: Biochim Biophys Acta. 2010 Feb;1797(2):113-28
references.pmid: 19761752
references.citation: Cancer Res. 2011 Mar 1;71(5):1836-48
references.pmid: 21242281
references.citation: Cancer Cell. 2010 Mar 16;17(3):235-48
references.pmid: 20227038
references.citation: Carcinogenesis. 2008 Apr;29(4):673-80
references.pmid: 17942460