Poly(ADP-ribose) polymerase-1 protects excessive DNA strand breaks from deterioration during repair in human cell extracts.

Parsons, Jason L. and Dianova, Irina I. and Allinson, Sarah L. and Dianov, Grigory L. (2005) Poly(ADP-ribose) polymerase-1 protects excessive DNA strand breaks from deterioration during repair in human cell extracts. FEBS Journal, 272 (8). pp. 2012-2021. ISSN 1742-464X

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Abstract

Base excision repair (BER), a major pathway for the removal of simple lesions in DNA, requires the co-ordinated action of several repair and ancillary proteins, the impairment of which can lead to genetic instability. We here address the role of poly(ADP-ribose) polymerase-1 (PARP-1) in BER. Using an in vitro cross-linking assay, we reveal that PARP-1 is always involved in repair of a uracil-containing oligonucleotide and that it binds to the damaged DNA during the early stages of repair. Inhibition of PARP-1 poly(ADP-ribosyl)ation by 3-aminobenzamide blocks dissociation of PARP-1 from damaged DNA and prevents further repair. We find that excessive poly(ADP-ribosyl)ation occurs when repair intermediates containing single-strand breaks are in excess of the repair capacity of the cell extract, suggesting that repeated binding of PARP-1 to the nicked DNA occurs. We also find increased sensitivity of repair intermediates to nuclease cleavage in PARP-deficient mouse fibroblasts and after depletion of PARP-1 from HeLa whole cell extracts. Our data support the model in which PARP-1 binding to DNA single-strand breaks or repair intermediates plays a protective role when repair is limited.

Item Type:
Journal Article
Journal or Publication Title:
FEBS Journal
Uncontrolled Keywords:
/dk/atira/pure/researchoutput/libraryofcongress/qh301
Subjects:
ID Code:
10158
Deposited By:
Deposited On:
08 Jul 2008 12:06
Refereed?:
Yes
Published?:
Published
Last Modified:
03 Nov 2020 13:46