Role of Oxidation of XRCC1 Protein in Regulation of Mammalian DNA Repair Process

Doklady. Biochemistry and Biophysics
I A Vasil'evaO I Lavrik

Abstract

The influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP-ribose)polymerases (PARP1 and PARP2) was studied for the first time. XRCC1, PARP1, and PARP2, functioning as scaffold proteins, are responsible for coordination of multistep repair of most abundant DNA lesions. We showed that the XRCC1 oxidation reduces the efficiency of its ADP-ribosylation and the protein affinity for poly(ADP-ribose). The ADP-ribose modification of various XRCC1 forms is enhanced in the presence of DNA polymerase β (Polβ), capable of forming a stable complex with XRCC1. Oxidation suppresses the inhibitory effect of XRCC1 and its complex with Polβ on the automodification of PARP1 and PARP2, which may enhance the efficiency of repair. The results of this study indicate that the oxidation of XRCC1 plays a role in fine regulation of poly(ADP-ribosyl)ation levels of proteins and their coordinating functions in DNA repair.

References

Oct 30, 1986·Biochemical and Biophysical Research Communications·Y OhashiA Matsukage
May 1, 1993·Protein Science : a Publication of the Protein Society·M Wunderlich, R Glockshuber
Jul 23, 2013·DNA Repair·Julie K HortonSamuel H Wilson
Aug 13, 2013·PloS One·Ekaterina A BelousovaOlga I Lavrik
Mar 22, 2015·DNA Repair·Robert E London
Nov 29, 2016·Free Radical Biology & Medicine·Rachel Abbotts, David M Wilson
Feb 10, 2017·Free Radical Biology & Medicine·Julie K HortonSamuel H Wilson
Oct 16, 2018·Biochimica Et Biophysica Acta. Proteins and Proteomics·Inna A Vasil'evaOlga I Lavrik

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Citations

Jun 4, 2020·DNA Repair·Svetlana Khodyreva, Olga Lavrik

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Methods Mentioned

BETA
electrophoresis
X-ray
PARylation

Software Mentioned

Quantity One

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