Identification of an XRCC1 DNA binding activity essential for retention at sites of DNA damage

Scientific Reports
Mac C Y MokMurray S Junop

Abstract

Repair of two major forms of DNA damage, single strand breaks and base modifications, are dependent on XRCC1. XRCC1 orchestrates these repair processes by temporally and spatially coordinating interactions between several other repair proteins. Here we show that XRCC1 contains a central DNA binding domain (CDB, residues 219-415) encompassing its first BRCT domain. In contrast to the N-terminal domain of XRCC1, which has been reported to mediate damage sensing in vitro, we demonstrate that the DNA binding module identified here lacks binding specificity towards DNA containing nicks or gaps. Alanine substitution of residues within the CDB of XRCC1 disrupt DNA binding in vitro and lead to a significant reduction in XRCC1 retention at DNA damage sites without affecting initial recruitment. Interestingly, reduced retention at sites of DNA damage is associated with an increased rate of repair. These findings suggest that DNA binding activity of XRCC1 plays a significant role in retention at sites of damage and the rate at which damage is repaired.

References

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Datasets Mentioned

BETA
BC023593

Methods Mentioned

BETA
PCR
ion exchange chromatography
size exclusion chromatography
X-ray
dynamic light scattering
NMR

Software Mentioned

DAMMIN
Sigmaplot
Primus
GraphPad Prism
MONSA
Object Counter
SAXSLab
ImageJ
Volume Viewer
ATSAS

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