XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair

Whitehouse, Claire J, Taylor, Richard M, Thistlethwaite, Angela, Zhang, Hong, Karimi-Busheri, Feridoun, Lasko, Dana D, Weinfeld, Michael and Caldecott, Keith W (2001) XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell, 104 (1). pp. 107-117. ISSN 0092-8674

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Abstract

XRCC1 protein is required for DNA single-strand break repair and genetic stability but its biochemical role is unknown. Here, we report that XRCC1 interacts with human polynucleotide kinase in addition to its established interactions with DNA polymerase-ß and DNA ligase III. Moreover, these four proteins are coassociated in multiprotein complexes in human cell extract and together they repair single-strand breaks typical of those induced by reactive oxygen species and ionizing radiation. Strikingly, XRCC1 stimulates the DNA kinase and DNA phosphatase activities of polynucleotide kinase at damaged DNA termini and thereby accelerates the overall repair reaction. These data identify a novel pathway for mammalian single-strand break repair and demonstrate a concerted role for XRCC1 and PNK in the initial step of processing damaged DNA ends

Item Type: Article
Additional Information: This work is largely (>90%) from my lab. One panel of one figure was provided by an external collaborator (M.W). Reported discovery of a polynucloetide kinase in repair of double strand breaks.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: EPrints Services
Date Deposited: 06 Feb 2012 19:42
Last Modified: 30 Mar 2012 11:03
URI: http://sro.sussex.ac.uk/id/eprint/21825
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