Interaction with OGG1 is Required for Efficient Recruitment of XRCC1 to Base Excision Repair and Maintenance of Genetic Stability After Exposure to Oxidative Stress

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2015 Mar 4

PMID 25733688

Citations 29

Authors

Anna Campalans

Eva Moritz

Thierry Kortulewski

Denis Biard

Bernd Epe

J Pablo Radicella

Affiliations

Soon will be listed here.

Abstract

XRCC1 is an essential protein required for the maintenance of genomic stability through its implication in DNA repair. The main function of XRCC1 is associated with its role in the single-strand break (SSB) and base excision repair (BER) pathways that share several enzymatic steps. We show here that the polymorphic XRCC1 variant R194W presents a defect in its interaction with the DNA glycosylase OGG1 after oxidative stress. While proficient for single-strand break repair (SSBR), this variant does not colocalize with OGG1, reflecting a defect in its involvement in BER. Consistent with a role of XRCC1 in the coordination of the BER pathway, induction of oxidative base damage in XRCC1-deficient cells complemented with the R194W variant results in increased genetic instability as revealed by the accumulation of micronuclei. These data identify a specific molecular role for the XRCC1-OGG1 interaction in BER and provide a model for the effects of the R194W variant identified in molecular cancer epidemiology studies.

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References

Bolte S, Cordelieres F . A guided tour into subcellular colocalization analysis in light microscopy. J Microsc. 2007; 224(Pt 3):213-32. DOI: 10.1111/j.1365-2818.2006.01706.x. View

Barnes D, Lindahl T . Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet. 2004; 38:445-76. DOI: 10.1146/annurev.genet.38.072902.092448. View

Caldecott K . Protein-protein interactions during mammalian DNA single-strand break repair. Biochem Soc Trans. 2003; 31(Pt 1):247-51. DOI: 10.1042/bst0310247. View

Goode E, Ulrich C, Potter J . Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002; 11(12):1513-30. View

Vidal A, Boiteux S, Hickson I, Radicella J . XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J. 2001; 20(22):6530-9. PMC: 125722. DOI: 10.1093/emboj/20.22.6530. View

Nazarkina Z, Khodyreva S, Marsin S, Lavrik O, Radicella J . XRCC1 interactions with base excision repair DNA intermediates. DNA Repair (Amst). 2006; 6(2):254-64. DOI: 10.1016/j.dnarep.2006.10.002. View

Dianova I, Sleeth K, Allinson S, Parsons J, Breslin C, Caldecott K . XRCC1-DNA polymerase beta interaction is required for efficient base excision repair. Nucleic Acids Res. 2004; 32(8):2550-5. PMC: 419455. DOI: 10.1093/nar/gkh567. View

Berquist B, Singh D, Fan J, Kim D, Gillenwater E, Kulkarni A . Functional capacity of XRCC1 protein variants identified in DNA repair-deficient Chinese hamster ovary cell lines and the human population. Nucleic Acids Res. 2010; 38(15):5023-35. PMC: 2926592. DOI: 10.1093/nar/gkq193. View

Radicella J, Dherin C, Desmaze C, Fox M, Boiteux S . Cloning and characterization of hOGG1, a human homolog of the OGG1 gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1997; 94(15):8010-5. PMC: 21547. DOI: 10.1073/pnas.94.15.8010. View

10.

Kohn K, Erickson L, Ewig R, Friedman C . Fractionation of DNA from mammalian cells by alkaline elution. Biochemistry. 1976; 15(21):4629-37. DOI: 10.1021/bi00666a013. View

11.

Campalans A, Kortulewski T, Amouroux R, Menoni H, Vermeulen W, Radicella J . Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair. Nucleic Acids Res. 2013; 41(5):3115-29. PMC: 3597691. DOI: 10.1093/nar/gkt025. View

12.

Okano S, Kanno S, Nakajima S, Yasui A . Cellular responses and repair of single-strand breaks introduced by UV damage endonuclease in mammalian cells. J Biol Chem. 2000; 275(42):32635-41. DOI: 10.1074/jbc.M004085200. View

13.

Wilson S, Kunkel T . Passing the baton in base excision repair. Nat Struct Biol. 2000; 7(3):176-8. DOI: 10.1038/73260. View

14.

Kim J, Krasieva T, Kurumizaka H, Chen D, Taylor A, Yokomori K . Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells. J Cell Biol. 2005; 170(3):341-7. PMC: 2171485. DOI: 10.1083/jcb.200411083. View

15.

Caldecott K . XRCC1 and DNA strand break repair. DNA Repair (Amst). 2003; 2(9):955-69. DOI: 10.1016/s1568-7864(03)00118-6. View

16.

Takanami T, Nakamura J, Kubota Y, Horiuchi S . The Arg280His polymorphism in X-ray repair cross-complementing gene 1 impairs DNA repair ability. Mutat Res. 2005; 582(1-2):135-45. DOI: 10.1016/j.mrgentox.2005.01.007. View

17.

Tebbs R, Flannery M, Meneses J, Hartmann A, Tucker J, Thompson L . Requirement for the Xrcc1 DNA base excision repair gene during early mouse development. Dev Biol. 1999; 208(2):513-29. DOI: 10.1006/dbio.1999.9232. View

18.

Caldecott K, Aoufouchi S, Johnson P, Shall S . XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro. Nucleic Acids Res. 1996; 24(22):4387-94. PMC: 146288. DOI: 10.1093/nar/24.22.4387. View

19.

Ladiges W, Wiley J, MacAuley A . Polymorphisms in the DNA repair gene XRCC1 and age-related disease. Mech Ageing Dev. 2003; 124(1):27-32. DOI: 10.1016/s0047-6374(02)00166-5. View

20.

Brem R, Hall J . XRCC1 is required for DNA single-strand break repair in human cells. Nucleic Acids Res. 2005; 33(8):2512-20. PMC: 1088068. DOI: 10.1093/nar/gki543. View