Report

Protein phosphatase PP4 is involved in NHEJ-mediated repair of DNA double-strand breaks

Volume 11, Issue 14   July 15, 2012
Pages 2643 - 2649
http://dx.doi.org/10.4161/cc.20957
Keywords: DNA double-strand break repair, DNA repair, KAP1, nonhomologous end joining, protein phosphatase PP4
Authors: Jinping Liu, Linli Xu, Jianing Zhong, Ji Liao, Jing Li and Xingzhi Xu

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Abstract:
Reversible phosphorylation is an essential posttranslational modification to turn on/off a protein function and to regulate many cellular activities, including DNA repair. A DNA double-strand break (DSB) is the most lethal form of DNA damage and is mainly fixed by the error-prone nonhomologous end joining (NHEJ)-mediated repair and by the high-fidelity homology recombination (HR)-mediated repair. We found previously that protein phosphatase PP4 is required for HR-mediated DSB repair. In this report, we showed that depletion of PP4C by siRNA compromised NHEJ-mediated repair of DSBs induced by the nuclease I-SceI. Both PP4C and its regulatory subunit PP4R2 physically interacted with the chromatin condensation factor KAP1 (KRAB-associated protein 1). Depletion of PP4C led to sustained phosphorylation of KAP1 at Ser824. Conversely, overexpression of PP4C resulted in a decrease of KAP1 phosphorylation. PP4 dephosphorylated pKAP1 in vitro. Inhibition of KAP1 expression resulted in a defect on NHEJ-mediated DSB repair, and co-depletion of PP4c and KAP1 did not have significant synergistic effect on NHEJ-mediated DSB repair. Taken together, our results suggest that PP4C and KAP1 are in the same epistasis group, and PP4 is involved in NHEJ-mediated DSB repair, possibly through regulating the phosphorylation status of KAP1.

Received: April 21, 2012; Accepted: May 31, 2012

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