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