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PMID: 17548475 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase.

Molecular and cellular biology ·Vol. 27 ·No. 15 ·2007-08-00 ·Pages 5597-605

Fisher AE, Hochegger H, Takeda S, Caldecott KW

Abstract

Single-strand breaks are the commonest lesions arising in cells, and defects in their repair are implicated in neurodegenerative disease. One of the earliest events during single-strand break repair (SSBR) is the rapid synthesis of poly(ADP-ribose) (PAR) by poly(ADP-ribose) polymerase (PARP), followed by its rapid degradation by poly(ADP-ribose) glycohydrolase (PARG). While the synthesis of poly(ADP-ribose) is important for rapid rates of chromosomal SSBR, the relative importance of poly(ADP-ribose) polymerase 1 (PARP-1) and PARP-2 and of the subsequent degradation of PAR by PARG is unclear. Here we have quantified SSBR rates in human A549 cells depleted of PARP-1, PARP-2, and PARG, both separately and in combination. We report that whereas PARP-1 is critical for rapid global rates of SSBR in human A549 cells, depletion of PARP-2 has only a minor impact, even in the presence of depleted levels of PARP-1. Moreover, we identify PARG as a novel and critical component of SSBR that accelerates this process in concert with PARP-1.

MeSH Terms
Animals Cell Line, Tumor Chickens DNA Breaks, Single-Stranded DNA Repair/drug effects DNA-Binding Proteins/metabolism Glycoside Hydrolases/deficiency,metabolism HeLa Cells Histones/metabolism Humans Hydrogen Peroxide/pharmacology Oxidative Stress/drug effects Poly(ADP-ribose) Polymerases/metabolism X-ray Repair Cross Complementing Protein 1
Chemicals
DNA-Binding Proteins H2AX protein, human Histones X-ray Repair Cross Complementing Protein 1 Hydrogen Peroxide Poly(ADP-ribose) Polymerases Glycoside Hydrolases poly ADP-ribose glycohydrolase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fisher Anna E O
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom.
Hochegger Helfrid
Takeda Shunichi
Caldecott Keith W
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.02248-06
Published
2007-08-00
Epub
2007-00-04
Pages
5597-605
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1952076
Subset
IM
Grants
Medical Research Council · G0001259 · United Kingdom
Medical Research Council · G0600776 · United Kingdom
External Links
PubMed source DOI: 10.1128/MCB.02248-06 PMC Full Text View journal details
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