Efficient single-strand break repair requires binding to both poly(ADP-Ribose) and DNA by the central BRCT domain of XRCC1
Author(s)
Type
Journal Article
Abstract
XRCC1 accelerates repair of DNA single-strand breaks by acting as a scaffold protein for the recruitment of Polβ, LigIIIα, and end-processing factors, such as PNKP and APTX. XRCC1 itself is recruited to DNA damage through interaction of its central BRCT domain with poly(ADP-ribose) chains generated by PARP1 or PARP2. XRCC1 is believed to interact directly with DNA at sites of damage, but the molecular basis for this interaction within XRCC1 remains unclear. We now show that the central BRCT domain simultaneously mediates interaction of XRCC1 with poly(ADP-ribose) and DNA, through separate and non-overlapping binding sites on opposite faces of the domain. Mutation of residues within the DNA binding site, which includes the site of a common disease-associated human polymorphism, affects DNA binding of this XRCC1 domain in vitro and impairs XRCC1 recruitment and retention at DNA damage and repair of single-strand breaks in vivo.
Date Issued
2019-01-15
Date Acceptance
2018-12-18
Citation
Cell Reports, 2019, 26 (3), pp.573-581.e5
ISSN
2211-1247
Publisher
Elsevier
Start Page
573
End Page
581.e5
Journal / Book Title
Cell Reports
Volume
26
Issue
3
Copyright Statement
© 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Wellcome Trust
Imperial College Trust
Wellcome Trust
Wellcome Trust
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000455627400008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
057259/Z/99/Z
ICTRUSTP47774
085464/Z/08/Z
202926/Z/16/Z
MR/P028225/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
BASE EXCISION-REPAIR
LUNG-CANCER PATIENTS
PROTEIN XRCC1
GENE POLYMORPHISMS
POLYMERASE BETA
RISK-FACTOR
ADP-RIBOSE
DAMAGE
RECOGNITION
ALLELE
Publication Status
Published
Date Publish Online
2019-01-15