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Molecular and Cellular Biology, January 2000, p. 735-740, Vol. 20, No. 2
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A Cell Cycle-Specific Requirement for the XRCC1
BRCT II Domain during Mammalian DNA Strand Break Repair
Richard M.
Taylor,
David J.
Moore,
Jenna
Whitehouse,
Penny
Johnson, and
Keith W.
Caldecott*
School of Biological Sciences, University of
Manchester, Manchester M13 9PT, United Kingdom
Received 1 June 1999/Returned for modification 20 July
1999/Accepted 13 October 1999
XRCC1 protein is essential for viability in mammals and is required
for efficient DNA single-strand break repair and genetic stability
following DNA base damage. We report here that XRCC1-dependent strand
break repair in G1 phase of the cell cycle is abolished by
mutations created within the XRCC1 BRCT domain that interact with DNA
ligase III. In contrast, XRCC1-dependent DNA strand break repair in S
phase is largely unaffected by these mutations. These data describe a
cell cycle-specific role for a BRCT domain, and we conclude that the
XRCC1-DNA ligase III complex is required for DNA strand break repair in
G1 phase of the cell cycle but is dispensable for this
process in S phase. The S-phase DNA repair process can remove both
strand breaks induced in S phase and those that persist from
G1 and can in part compensate for lack of repair in
G1. This process correlates with the appearance of XRCC1
nuclear foci that colocalize with Rad51 and may thus function in
concert with homologous recombination.
*
Corresponding author. Mailing address: School of
Biological Sciences, G.38 Stopford Bldg., University of Manchester,
Oxford Rd., Manchester M13 9PT, United Kingdom. Phone: 0161 275 5311. Fax: 0161 275 5600. E-mail:
keith.caldecott{at}man.ac.uk.
Molecular and Cellular Biology, January 2000, p. 735-740, Vol. 20, No. 2
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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