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Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair

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posted on 2023-06-08, 09:49 authored by Richard M Taylor, Angela Thistlethwaite, Keith CaldecottKeith Caldecott
The DNA single-strand break repair (SSBR) protein XRCC1 is required for genetic stability and for embryonic viability. XRCC1 possesses two BRCA1 carboxyl-terminal (BRCT) protein interaction domains, denoted BRCT I and II. BRCT II is required for SSBR during G1 but is dispensable for this process during S/G2 and consequently for cell survival following DNA alkylation. Little is known about BRCT I, but this domain has attracted considerable interest because it is the site of a genetic polymorphism that epidemiological studies have associated with altered cancer risk. We report that the BRCT I domain comprises the evolutionarily conserved core of XRCC1 and that this domain is required for efficient SSBR during both G1 and S/G2 cell cycle phases and for cell survival following treatment with methyl methanesulfonate. However, the naturally occurring human polymorphism in BRCT I supported XRCC1-dependent SSBR and cell survival after DNA alkylation equally well. We conclude that while the BRCT I domain is critical for XRCC1 to maintain genetic integrity and cell survival, the polymorphism does not impact significantly on this function and therefore is unlikely to impact significantly on susceptibility to cancer.

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular and Cellular Biology

ISSN

0270-7306

Publisher

American Society for Microbiology

Issue

8

Volume

22

Page range

2556-2563.

Pages

8.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Notes

From SRO Other: R. M. Taylor (Can't identify)

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

First Open Access (FOA) Date

2016-03-22

First Compliant Deposit (FCD) Date

2016-11-16

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