Poly(ADP-ribose) polymerase in base excision repair: always engaged, but not essential for DNA damage processing.

Allinson, Sarah L. and Dianova, Irina I. and Dianov, Grigory L. (2003) Poly(ADP-ribose) polymerase in base excision repair: always engaged, but not essential for DNA damage processing. Acta Biochimica Polonica, 50 (1). pp. 169-179. ISSN 0001-527X

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Abstract

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.

Item Type:
Journal Article
Journal or Publication Title:
Acta Biochimica Polonica
Uncontrolled Keywords:
/dk/atira/pure/researchoutput/libraryofcongress/qh301
Subjects:
?? DNA REPAIRBASE EXCISION REPAIRPARPABASIC SITESIN VITRO REPAIRCELL EXTRACTSBIOCHEMISTRY, GENETICS AND MOLECULAR BIOLOGY(ALL)QH301 BIOLOGY ??
ID Code:
10162
Deposited By:
Deposited On:
08 Jul 2008 10:58
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Sep 2023 03:43