Human Transcriptional Coactivator PC4 Stimulates DNA End Joining and Activates DSB Repair Activity

被引:32
作者
Batta, Kiran [1 ]
Yokokawa, Masatoshi [2 ]
Takeyasu, Kunio [2 ]
Kundu, Tapas K. [1 ]
机构
[1] Jawaharlal Nehru Ctr Adv Sci Res, Mol Bio,& Genet Unit, Transcript & Dis Lab, Jakkur 560064, PO Bangalore, India
[2] Kyoto Univ, Grad Sch Biostudies, Lab Plasma Membrane & Nucl Signaling, Sakyo Ku, Kyoto, Japan
关键词
end joining; DSB repair; PC4; atomic force microscopy; NHEJ; DOUBLE-STRAND BREAKS; DEPENDENT PROTEIN-KINASE; MOBILITY GROUP PROTEIN-1; MAMMALIAN-CELLS; P53; FUNCTION; COMPLEX; BINDING; XLF; KU; INTERACTS;
D O I
10.1016/j.jmb.2008.11.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human transcriptional coactivator PC4 is a highly abundant nuclear protein that is involved in diverse cellular processes ranging from transcription to chromatin organization. Earlier, we have shown that PC4, a positive activator of p53, overexpresses upon genotoxic insult in a p53-dependent manner. In the present study, we show that PC4 stimulates ligase-mediated DNA end joining irrespective of the source of DNA ligase. Pull-down assays reveal that PC4 helps in the association of DNA ends through its C-terminal domain. In vitro nonhomologous end-joining assays with cell-free extracts show that PC4 enhances the joining of noncomplementary DNA ends. Interestingly, we found that PC4 activates double-strand break (DSB) repair activity through stimulation of DSB rejoining in vivo. Together, these findings demonstrate PC4 as an activator of nonhomologous end joining and DSB repair activity. (C) 2008 Elsevier Ltd. All rights reserved.
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页码:788 / 799
页数:12
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