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Molecular and Cellular Biology, August 2007, p. 5597-5605, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.02248-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Poly(ADP-Ribose) Polymerase 1 Accelerates Single-Strand Break Repair in Concert with Poly(ADP-Ribose) Glycohydrolase{triangledown}

Anna E. O. Fisher,1 Helfrid Hochegger,2 Shunichi Takeda,2 and Keith W. Caldecott1*

Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom,1 Crest Laboratory, Department of Radiation Genetics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan2

Received 30 November 2006/ Returned for modification 21 December 2006/ Accepted 18 May 2007

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.

* Corresponding author. Mailing address: Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom. Phone: 44 (0) 1273 877519. Fax: 44 (0) 1273 678121. E-mail: k.w.caldecott{at}sussex.ac.uk

{triangledown} Published ahead of print on 4 June 2007.

Molecular and Cellular Biology, August 2007, p. 5597-5605, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.02248-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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