DNA Repair Endonuclease ERCC1-XPF As a Novel Therapeutic Target to Overcome Chemoresistance in Cancer Therapy

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2012 Sep 4

PMID 22941649

Citations 92

Authors

Ewan M McNeil

David W Melton

Affiliations

Soon will be listed here.

Abstract

The ERCC1-XPF complex is a structure-specific endonuclease essential for the repair of DNA damage by the nucleotide excision repair pathway. It is also involved in other key cellular processes, including DNA interstrand crosslink (ICL) repair and DNA double-strand break (DSB) repair. New evidence has recently emerged, increasing our understanding of its requirement in these additional roles. In this review, we focus on the protein-protein and protein-DNA interactions made by the ERCC1 and XPF proteins and discuss how these coordinate ERCC1-XPF in its various roles. In a number of different cancers, high expression of ERCC1 has been linked to a poor response to platinum-based chemotherapy. We discuss prospects for the development of DNA repair inhibitors that target the activity, stability or protein interactions of the ERCC1-XPF complex as a novel therapeutic strategy to overcome chemoresistance.

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References

Kwon H, Roh M, Oh S, Kim S, Kim M, Kim J . Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer. Ann Oncol. 2007; 18(3):504-9. DOI: 10.1093/annonc/mdl430. View

Motycka T, Bessho T, Post S, Sung P, Tomkinson A . Physical and functional interaction between the XPF/ERCC1 endonuclease and hRad52. J Biol Chem. 2004; 279(14):13634-9. DOI: 10.1074/jbc.M313779200. View

Su Y, Orelli B, Madireddy A, Niedernhofer L, Scharer O . Multiple DNA binding domains mediate the function of the ERCC1-XPF protein in nucleotide excision repair. J Biol Chem. 2012; 287(26):21846-55. PMC: 3381147. DOI: 10.1074/jbc.M111.337899. View

Nishino T, Komori K, Tsuchiya D, Ishino Y, Morikawa K . Crystal structure and functional implications of Pyrococcus furiosus hef helicase domain involved in branched DNA processing. Structure. 2005; 13(1):143-53. DOI: 10.1016/j.str.2004.11.008. View

Bennardo N, Cheng A, Huang N, Stark J . Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet. 2008; 4(6):e1000110. PMC: 2430616. DOI: 10.1371/journal.pgen.1000110. View

Gregg S, Robinson A, Niedernhofer L . Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. DNA Repair (Amst). 2011; 10(7):781-91. PMC: 3139823. DOI: 10.1016/j.dnarep.2011.04.026. View

Kirschner K, Melton D . Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs. Anticancer Res. 2010; 30(9):3223-32. View

Munoz P, Blanco R, Flores J, Blasco M . XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Nat Genet. 2005; 37(10):1063-71. DOI: 10.1038/ng1633. View

Dorjsuren D, Kim D, Maloney D, Wilson 3rd D, Simeonov A . Complementary non-radioactive assays for investigation of human flap endonuclease 1 activity. Nucleic Acids Res. 2010; 39(2):e11. PMC: 3025571. DOI: 10.1093/nar/gkq1082. View

10.

Choi Y, Ryu K, Ko Y, Chae Y, Pelton J, Wemmer D . Biophysical characterization of the interaction domains and mapping of the contact residues in the XPF-ERCC1 complex. J Biol Chem. 2005; 280(31):28644-52. DOI: 10.1074/jbc.M501083200. View

11.

Rai G, Vyjayanti V, Dorjsuren D, Simeonov A, Jadhav A, Wilson 3rd D . Synthesis, biological evaluation, and structure-activity relationships of a novel class of apurinic/apyrimidinic endonuclease 1 inhibitors. J Med Chem. 2012; 55(7):3101-12. PMC: 3515842. DOI: 10.1021/jm201537d. View

12.

Kelley L, Sternberg M . Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc. 2009; 4(3):363-71. DOI: 10.1038/nprot.2009.2. View

13.

Wood R . Mammalian nucleotide excision repair proteins and interstrand crosslink repair. Environ Mol Mutagen. 2010; 51(6):520-6. PMC: 3017513. DOI: 10.1002/em.20569. View

14.

van Duin M, de Wit J, Odijk H, Westerveld A, Yasui A, Koken M . Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10. Cell. 1986; 44(6):913-23. DOI: 10.1016/0092-8674(86)90014-0. View

15.

Sijbers A, de Laat W, Ariza R, Biggerstaff M, Wei Y, Moggs J . Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell. 1996; 86(5):811-22. DOI: 10.1016/s0092-8674(00)80155-5. View

16.

Wu Y, Zacal N, Rainbow A, Zhu X . XPF with mutations in its conserved nuclease domain is defective in DNA repair but functions in TRF2-mediated telomere shortening. DNA Repair (Amst). 2006; 6(2):157-66. DOI: 10.1016/j.dnarep.2006.09.005. View

17.

Bessho T, Sancar A, Thompson L, Thelen M . Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex. J Biol Chem. 1997; 272(6):3833-7. DOI: 10.1074/jbc.272.6.3833. View

18.

Newman M, Murray-Rust J, Lally J, Rudolf J, Fadden A, Knowles P . Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition. EMBO J. 2005; 24(5):895-905. PMC: 554130. DOI: 10.1038/sj.emboj.7600581. View

19.

Bowles M, Lally J, Fadden A, Mouilleron S, Hammonds T, McDonald N . Fluorescence-based incision assay for human XPF-ERCC1 activity identifies important elements of DNA junction recognition. Nucleic Acids Res. 2012; 40(13):e101. PMC: 3401468. DOI: 10.1093/nar/gks284. View

20.

Svendsen J, Smogorzewska A, Sowa M, OConnell B, Gygi S, Elledge S . Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009; 138(1):63-77. PMC: 2720686. DOI: 10.1016/j.cell.2009.06.030. View