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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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