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 0001-527XFull text not available from this repository.
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.
|Journal or Publication Title:||Acta Biochimica Polonica|
|Uncontrolled Keywords:||DNA repair ; base excision repair ; PARP ; abasic sites ; in vitro repair ; cell extracts|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Departments:||Faculty of Health and Medicine > Biomedical & Life Sciences|
|Deposited By:||Dr Sarah Allinson|
|Deposited On:||08 Jul 2008 11:58|
|Last Modified:||21 Jan 2017 01:06|
Actions (login required)