Human transcriptional coactivator PC4 stimulates DNA end joining and activates DSB repair activity.
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.
Batta
Kiran
K
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Jakkur, PO Bangalore 560064, India.
Yokokawa
Masatoshi
M
Takeyasu
Kunio
K
Kundu
Tapas K
TK
D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C509201:SUB1 protein, human; D014157:Transcription Factors; D004247:DNA