title: Interrogation of nucleotide excision repair capacity: impact on platinum-based cancer therapy.
abstract: DNA repair is essential for routine monitoring and repair of damage imparted to our genetic material by exposure to endogenous and exogenous carcinogens, including reactive oxygen species, UV light, and chemicals such as those found in cigarette smoke. Without DNA repair pathways, the continual assault on our DNA would be highly mutagenic and the risk of cancer increased. Paradoxically, the same pathways that help prevent cancer development are detrimental to the efficacy of DNA-damaging cancer therapeutics such as cisplatin. Recent studies demonstrate the inverse relationship between DNA repair capacity and efficacy of platinum-based chemotherapeutics: increased DNA repair capacity leads to resistance, while decreased capacity leads to increased sensitivities. Cisplatin's cytotoxic effects are mediated by formation of intrastrand DNA crosslinks, which are predominantly repaired via the nucleotide excision repair (NER) pathway. In an effort to personalize the treatment of cancers based on DNA repair capacity, we developed an ELISA-based assay to measure NER activity accurately and reproducibly as a prognostic for platinum-based treatments. Here we present an overview of DNA repair and its link to cancer and therapeutics. We also present data demonstrating the ability to detect the proteins of the pre-incision complex within the NER pathway from cell and tissue extracts.
authors.affiliation: Department of Medicine/Hematology and Oncology, Indiana University School of Medicine, 980 W. Walnut Street, Indianapolis, IN 46202, USA.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Earley
authors.forename: John J
authors.initials: JJ
authors.lastname: Turchi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010984:Platinum / Q000494:pharmacology / Q000627:therapeutic use; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D051716:Replication Protein A; D051760:Xeroderma Pigmentosum Group A Protein; D010984:Platinum; D002945:Cisplatin
references.citation: Annu Rev Biophys Biomol Struct. 1999;28:101-28
references.pmid: 10410797
references.citation: J Biol Chem. 1996 May 10;271(19):11047-50
references.pmid: 8626644
references.citation: Nat Struct Mol Biol. 2006 Mar;13(3):278-84
references.pmid: 16491090
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4592-5
references.pmid: 11904381
references.citation: Curr Biol. 1999 Mar 11;9(5):273-6
references.pmid: 10074455
references.citation: J Biol Chem. 1999 May 21;274(21):14972-8
references.pmid: 10329699
references.citation: Cell Mol Life Sci. 2009 Mar;66(6):981-93
references.pmid: 19153658
references.citation: Mutat Res. 1994 Oct 1;310(1):89-102
references.pmid: 7523888
references.citation: Curr Opin Genet Dev. 2008 Feb;18(1):80-6
references.pmid: 18343102
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6664-9
references.pmid: 9192622
references.citation: Nature. 1968 May 18;218(5142):652-6
references.pmid: 5655953
references.citation: Neuroscience. 2007 Apr 14;145(4):1318-29
references.pmid: 17092652
references.citation: Nucleic Acids Res. 1989 Oct 25;17(20):8073-91
references.pmid: 2554251
references.citation: Int J Cancer. 2009 Mar 1;124(5):999-1007
references.pmid: 19065660
references.citation: Annu Rev Biochem. 2010;79:181-211
references.pmid: 20192759
references.citation: Genes Dev. 2000 Feb 1;14(3):349-59
references.pmid: 10673506
references.citation: Cancer Res. 2010 May 1;70(9):3851-2; author reply 3852
references.pmid: 20406965
references.citation: J Biol Chem. 1994 Apr 15;269(15):11121-32
references.pmid: 8157639
references.citation: Methods. 2009 May;48(1):46-53
references.pmid: 19269328
references.citation: Biochemistry. 2000 May 30;39(21):6433-9
references.pmid: 10828957
references.citation: J Biol Chem. 1993 Apr 5;268(10):7147-54
references.pmid: 8463251
references.citation: EMBO J. 1997 Nov 3;16(21):6559-73
references.pmid: 9351836
references.citation: Cell Res. 2008 Jan;18(1):73-84
references.pmid: 18166977
references.citation: Mol Cell Biol. 2010 Jun;30(11):2708-23
references.pmid: 20368362
references.citation: EMBO J. 2009 Apr 22;28(8):1111-20
references.pmid: 19279666
references.citation: Science. 1994 Dec 23;266(5193):1959-60
references.pmid: 7801122
references.citation: Curr Med Chem Anticancer Agents. 2005 Jan;5(1):73-88
references.pmid: 15720263
references.citation: Cell. 1988 Apr 8;53(1):97-106
references.pmid: 3349527
references.citation: J Biol Chem. 1995 Feb 24;270(8):4152-7
references.pmid: 7876167
references.citation: Crit Rev Toxicol. 2009;39(8):679-94
references.pmid: 19743945
references.citation: N Engl J Med. 2006 Sep 7;355(10):983-91
references.pmid: 16957145
references.citation: Curr Opin Pulm Med. 2007 Jul;13(4):284-9
references.pmid: 17534174
references.citation: Mutat Res. 1990 May;235(3):171-80
references.pmid: 2342504
references.citation: Pharmacogenet Genomics. 2009 Aug;19(8):613-25
references.pmid: 19620936
references.citation: Annu Rev Biochem. 1997;66:61-92
references.pmid: 9242902
references.citation: Cell Res. 2008 Jan;18(1):85-98
references.pmid: 18157157
references.citation: Cancer Res. 2003 Mar 15;63(6):1311-6
references.pmid: 12649192
references.citation: Methods Mol Biol. 2002;203:179-94
references.pmid: 12073441
references.citation: Nat Rev Cancer. 2003 Mar;3(3):155-68
references.pmid: 12612651
references.citation: Carcinogenesis. 2006 Jan;27(1):117-22
references.pmid: 16000400
references.citation: J Biol Chem. 2001 Jun 22;276(25):22630-7
references.pmid: 11278662
references.citation: Clin Chim Acta. 2006 Jan;363(1-2):71-82
references.pmid: 16102740
references.citation: Nat Genet. 2002 Feb;30(2):227-32
references.pmid: 11818965
references.citation: Gene. 2000 Jan 11;241(2):193-204
references.pmid: 10675030
references.citation: Science. 1994 Dec 23;266(5193):1926-9
references.pmid: 7801115
references.citation: Int J Cancer. 2006 Aug 15;119(4):964-7
references.pmid: 16550608
references.citation: Biochemistry. 1997 May 20;36(20):5955-62
references.pmid: 9166765
references.citation: Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5874-9
references.pmid: 14676109
references.citation: J Biol Chem. 2002 May 3;277(18):16096-101
references.pmid: 11859086
references.citation: DNA Repair (Amst). 2007 Feb 4;6(2):265-9
references.pmid: 17194629
references.citation: Mutat Res. 2009 Jul 31;668(1-2):54-72
references.pmid: 19622404
references.citation: Mol Cell Biol. 2001 Apr;21(7):2281-91
references.pmid: 11259578
references.citation: Protein Expr Purif. 2000 Jun;19(1):1-11
references.pmid: 10833384
references.citation: J Biol Chem. 1997 Mar 21;272(12):7570-3
references.pmid: 9065408
references.citation: Biochem Pharmacol. 2000 Nov 1;60(9):1305-13
references.pmid: 11008124
references.citation: Ann Oncol. 1999;10 Suppl 1:87-92
references.pmid: 10219460
references.citation: Biochemistry. 2001 Mar 6;40(9):2901-10
references.pmid: 11258902
references.citation: Mol Cell. 2007 Apr 27;26(2):245-56
references.pmid: 17466626
references.citation: Science. 2009 Sep 11;325(5946):1319
references.pmid: 19745119
references.citation: Biochimie. 1999 Jan-Feb;81(1-2):39-44
references.pmid: 10214908
references.citation: Br J Cancer. 2009 Sep 1;101(5):816-21
references.pmid: 19672258