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A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage

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El-Khamisy, S. F.·2003·Nucleic Acids Research

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.

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Metadata

Authors
El-Khamisy, S. F.
Venue
Nucleic Acids Research
Published
2003-10-01
Volume
31
Issue
19
Pages
5526-5533
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2168891239
Cited by
659
References
41
FWCI
5.79
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. https://app.cochat.ai/papers/10.1093/nar/gkg761
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El-Khamisy, S. F. (2003). A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Research. https://doi.org/10.1093/nar/gkg761

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