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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 CaldecottXRCC1 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
CellISSN
0092-8674External DOI
Issue
1Volume
104Page range
107-117Pages
11.0Department 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
2012-02-06Usage metrics
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