Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 27, Issue 15, Pages 5597-5605Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.02248-06
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Funding
- Medical Research Council [G0001259, G0600776] Funding Source: Medline
- MRC [G0600776, G0001259] Funding Source: UKRI
- Medical Research Council [G0300662B, G0600776, G0001259] Funding Source: researchfish
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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.
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