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

journal contribution
posted on 2023-06-07, 23:46 authored by Claire J Whitehouse, Richard M Taylor, Angela Thistlethwaite, Hong Zhang, Feridoun Karimi-Busheri, Dana D Lasko, Michael Weinfeld, Keith CaldecottKeith Caldecott
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

History

Publication status

  • Published

Journal

Cell

ISSN

0092-8674

Issue

1

Volume

104

Page range

107-117

Pages

11.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Notes

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.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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