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Efficient single-strand break repair requires binding to both poly(ADP-ribose) and DNA by the central BRCT domain of XRCC1
journal contribution
posted on 2023-06-09, 16:35 authored by Luis M Polo, Yingqi Xu, Peter Hornyak, Fernando Garces, Zhihong Zeng, Richard Hailstone, Steve J Matthews, Keith CaldecottKeith Caldecott, Antony OliverAntony Oliver, Laurence PearlLaurence PearlXRCC1 accelerates repair of DNA single-strand breaks by acting as a scaffold protein for the recruitment of Pol-beta, LigIII-alpha 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.
Funding
Chromosomal Single-strand break Repair: Mechanisms & Degenerative Disease; G0830; MRC-MEDICAL RESEARCH COUNCIL; MR/J006750/1
Structural Biology of DNA Damage Response and Repair Mechanisms and its Exploitation for Drug Discov; G0891; CANCER RESEARCH UK; C302/A14532
Structural Biology of DNA Damage Response and Repair Mechanisms; G2176; CANCER RESEARCH UK; C302/A24386
History
Publication status
- Published
File Version
- Published version
Journal
Cell ReportsISSN
2211-1247Publisher
ElsevierExternal DOI
Issue
3Volume
26Page range
573-581.e5Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-02-05First Open Access (FOA) Date
2019-02-05First Compliant Deposit (FCD) Date
2019-02-05Usage metrics
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