A requirement for PARP‐1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage
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TLDR
The 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).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.read more
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References
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Journal ArticleDOI
XRCC1 Is Specifically Associated with Poly(ADP-Ribose) Polymerase and Negatively Regulates Its Activity following DNA Damage
Murielle Masson,Claude Niedergang,Valérie Schreiber,Sylviane Muller,Josiane Ménissier-de Murcia,Gilbert de Murcia +5 more
TL;DR: The results provide strong evidence that PARP is a member of a BER multiprotein complex involved in the detection of DNA interruptions and possibly in the recruitment of XRCC1 and its partners for efficient processing of these breaks in a coordinated manner.
Journal ArticleDOI
Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein.
TL;DR: Data indicate that XRCC1, which has no known catalytic activity, might serve as a scaffold protein during base excision‐repair, allowing for more efficient ligation after filling of a single nucleotide patch.
Journal ArticleDOI
Poly(ADP-ribose) Polymerase-2 (PARP-2) Is Required for Efficient Base Excision DNA Repair in Association with PARP-1 and XRCC1
Valérie Schreiber,Jean-Christophe Amé,Pascal Dollé,Inès Schultz,Bruno Rinaldi,Valérie Fraulob,Josiane Ménissier-de Murcia,Gilbert de Murcia +7 more
TL;DR: Following treatment by the alkylating agentN-nitroso-N-methylurea (MNU),PARP-2-deficient cells displayed an important delay in DNA strand breaks resealing, similar to that observed in PARP-1 deficient cells, thus confirming that PARp-2 is also an active player in base excision repair despite its low capacity to synthesize ADP-ribose polymers.
Journal ArticleDOI
DNA-bound structures and mutants reveal abasic DNA binding by APE1 DNA repair and coordination
TL;DR: Structural and mutational results show how APE1 probably displaces bound glycosylases and retains the nicked DNA product, suggesting that APe1 acts in vivo to coordinate the orderly transfer of unstable DNA damage intermediates between the excision and synthesis steps of DNA repair.
Journal ArticleDOI
XRCC1 Polypeptide Interacts with DNA Polymerase β and Possibly Poly (ADP-Ribose) Polymerase, and DNA Ligase III Is a Novel Molecular ‘Nick-Sensor’ In Vitro
TL;DR: It is demonstrated that XRCC1 is additionally associated with DNA polymerase-beta in human cells and that these polypeptides also directly interact, and data suggesting that poly (ADP-ribose) polymerase can interact with XR CC1 are presented.