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2003 | 50 | 1 | 169-179
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Poly(ADP-ribose) polymerase in base excision repair: always engaged, but not essential for DNA damage processing.

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Poly(ADP-ribose) polymerase (PARP-1) is an abundant nuclear protein with a high affinity for single- and double-strand DNA breaks. Its binding to strand breaks promotes catalysis of the covalent modification of nuclear proteins with poly(ADP-ribose) synthesised from NAD+. PARP-1-knockout cells are extremely sensitive to alkylating agents, suggesting the involvement of PARP-1 in base excision repair; however, its role remains unclear. We investigated the dependence of base excision repair pathways on PARP-1 and NAD+ using whole cell extracts derived from normal and PARP-1 deficient mouse cells and DNA substrates containing abasic sites. In normal extracts the rate of repair was highly dependent on NAD+. We found that in the absence of NAD+ repair was slowed down 4-6-fold after incision of the abasic site. We also established that in extracts from PARP-1 deficient mouse cells, repair of both regular and reduced abasic sites was increased with respect to normal extracts and was NAD+-independent, suggesting that in both short- and long-patch BER PARP-1 slows down, rather than stimulates, the repair reaction. Our data support the proposal that PARP-1 does not play a major role in catalysis of DNA damage processing via either base excision repair pathway.
Physical description
  • MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire, OX11 0RD, U.K.
  • MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire, OX11 0RD, U.K.
  • MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire, OX11 0RD, U.K.
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