Title |
Poly(ADP-ribose) Polymerase-2 (PARP-2) Is Required for Efficient Base Excision DNA Repair in Association with PARP-1 and XRCC1*
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Published in |
Journal of Biological Chemistry, April 2002
|
DOI | 10.1074/jbc.m202390200 |
Pubmed ID | |
Authors |
Valérie Schreiber, Jean-Christophe Amé, Pascal Dollé, Inès Schultz, Bruno Rinaldi, Valérie Fraulob, Josiane Ménissier-de Murcia, Gilbert de Murcia |
Abstract |
The DNA damage dependence of poly(ADP-ribose) polymerase-2 (PARP-2) activity is suggestive of its implication in genome surveillance and protection. Here we show that the PARP-2 gene, mainly expressed in actively dividing tissues follows, but to a smaller extent, that of PARP-1 during mouse development. We found that PARP-2 and PARP-1 homo- and heterodimerize; the interacting interfaces, sites of reciprocal modification, have been mapped. PARP-2 was also found to interact with three other proteins involved in the base excision repair pathway: x-ray cross complementing factor 1 (XRCC1), DNA polymerase beta, and DNA ligase III, already known as partners of PARP-1. XRCC1 negatively regulates PARP-2 activity, as it does for PARP-1, while being a polymer acceptor for both PARP-1 and PARP-2. To gain insight into the physiological role of PARP-2 in response to genotoxic stress, we developed by gene disruption mice deficient in PARP-2. Following treatment by the alkylating agent N-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. |
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Geographical breakdown
Country | Count | As % |
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United Kingdom | 3 | 1% |
United States | 3 | 1% |
India | 1 | <1% |
Ireland | 1 | <1% |
Unknown | 231 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 67 | 28% |
Student > Master | 34 | 14% |
Student > Bachelor | 28 | 12% |
Researcher | 27 | 11% |
Student > Doctoral Student | 12 | 5% |
Other | 33 | 14% |
Unknown | 38 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 81 | 34% |
Biochemistry, Genetics and Molecular Biology | 66 | 28% |
Medicine and Dentistry | 26 | 11% |
Chemistry | 7 | 3% |
Neuroscience | 5 | 2% |
Other | 10 | 4% |
Unknown | 44 | 18% |