Interaction with OGG1 is required for efficient recruitment of XRCC1 to base excision repair and maintenance of genetic stability after exposure to oxidative stress

Molecular and Cellular Biology
Anna CampalansJ P Radicella

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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Citations

Mar 5, 2016·Neural Plasticity·Laura NarcisoEugenia Dogliotti
Jan 10, 2017·Nature Communications·Melike ÇağlayanSamuel H Wilson
Aug 11, 2018·PloS One·Michelle L DuquetteMichael W Berns
Jul 30, 2015·The Journal of Biological Chemistry·Ranjana PalAlain Nepveu
Dec 21, 2016·The Journal of Biological Chemistry·Carolina L BigarellaSaghi Ghaffari
Sep 4, 2016·The Journal of Biological Chemistry·Simran KaurAlain Nepveu
Sep 26, 2020·Frontiers in Public Health·Renata SistoPieranna Chiarella
Sep 16, 2020·BMC Genomics·Natalia RubanovaNadya Morozova
Jul 18, 2019·DNA Repair·Harini Sampath, R Stephen Lloyd
Dec 4, 2019·DNA Repair·Agnes K JanoshaziSamuel H Wilson

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