A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage
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Open Access
- 1 October 2003
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 31 (19) , 5526-5533
- https://doi.org/10.1093/nar/gkg761
Abstract
The molecular role of poly (ADP‐ribose) polymerase‐1 in DNA repair is unclear. Here, we show that the single‐strand break repair protein XRCC1 is rapidly assembled into discrete nuclear foci after oxidative DNA damage at sites of poly (ADP‐ribose) synthesis. Poly (ADP‐ribose) synthesis peaks during a 10 min treatment with H2O2 and the appearance of XRCC1 foci peaks shortly afterwards. Both sites of poly (ADP‐ribose) and XRCC1 foci decrease to background levels during subsequent incubation in drug‐free medium, consistent with the rapidity of the single‐strand break repair process. The formation of XRCC1 foci at sites of poly (ADP‐ribose) was greatly reduced by mutation of the XRCC1 BRCT I domain that physically interacts with PARP‐1. Moreover, we failed to detect XRCC1 foci in Adprt1–/– MEFs after treatment with H2O2. These data demonstrate that PARP‐1 is required for the assembly or stability of XRCC1 nuclear foci after oxidative DNA damage and suggest that the formation of these foci is mediated via interaction with poly (ADP‐ribose). These results support a model in which the rapid activation of PARP‐1 at sites of DNA strand breakage facilitates DNA repair by recruiting the molecular scaffold protein, XRCC1.Keywords
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