期刊
CELL CYCLE
卷 11, 期 14, 页码 2643-2649出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.20957
关键词
protein phosphatase PP4; DNA double-strand break repair; nonhomologous end joining; KAP1; DNA repair
类别
资金
- National Natural Science Foundation of China [31130017, 31071190, 30711120570, 30700420]
- 973 project [2010CB911904]
- Jurisdiction of Beijing Municipality [PHR20110508]
- Beijing Nova Program [2007B062]
- Beijing Natural Science Foundation
- Beijing Municipal Commission of Education [KM200910028012]
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 PP 4 is required for HR-mediated DSB repair. In this report, we showed that depletion of PP 4C by siRNA compromised NHEJ-mediated repair of DSBs induced by the nuclease I-SceI. Both PP 4C and its regulatory subunit PP 4R2 physically interacted with the chromatin condensation factor KAP1 (KRAB-associated protein 1). Depletion of PP 4C led to sustained phosphorylation of KAP1 at Ser824. Conversely, overexpression of PP 4C resulted in a decrease of KAP1 phosphorylation. PP 4 dephosphorylated pKAP1 in vitro. Inhibition of KAP1 expression resulted in a defect on NHEJ-mediated DSB repair, and co-depletion of PP 4C and KAP1 did not have significant synergistic effect on NHEJ-mediated DSB repair. Taken together, our results suggest that PP 4C and KAP1 are in the same epistasis group, and PP 4 is involved in NHEJ-mediated DSB repair, possibly through regulating the phosphorylation status of KAP1.
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