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In p53-TAD KO cells, the p53-regulated DNA repair proteins xeroderma pigmentosum group A, DNA polymerase H, and DNA-binding protein 2 expression were found to be reduced compared with p53 wild-type cells. Exposure to a low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) as measured by RAD50 and MRE11 expression, checkpoint kinase 2 activation, and \u03b3H2A.X recruitment at DNA strand breaks in both cell groups, indicating that silence of p53-TAD does not affect the DDR mechanism upstream of p53. After removal of Doxo, p53 wild-type hiPSCs underwent DNA repair, corrected their damaged DNA, and restored DNA integrity. Conversely, p53-TAD KO hiPSCs did not undergo complete DNA repair and failed to restore DNA integrity. More importantly, continuous culture of p53-TAD KO hiPSCs underwent G<jats:sub>2<\/jats:sub>\/M cell cycle arrest and expressed the cellular senescent marker p16<jats:sup>INK4a<\/jats:sup>. Our data clearly show that silence of the TAD of p53 did not affect DDR but affected the DNA repair process, implying the crucial role of p53-TAD in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent cellular senescence. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY The p53 transactivation domain (TAD) in human induced pluripotent stem cells (iPSCs) was deleted using the CRISPR\/Cas9 system. Deletion of p53-TAD resulted in increased cell proliferation but did not affect iPSC pluripotency. DNA repair machinery upstream of p53 was not affected in p53-TAD knockout, but p53-regulated DNA repair proteins xeroderma pigmentosum group A, DNA polymerase H, and DNA-binding protein 2 were affected. Finally, p53-TAD was found to be necessary for iPSCs to repair damaged DNA and retain DNA integrity. <\/jats:p>","DOI":"10.1152\/ajpheart.00160.2018","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T16:13:39Z","timestamp":1526660019000},"page":"H512-H521","source":"Crossref","is-referenced-by-count":11,"title":["Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells"],"prefix":"10.1152","volume":"315","author":[{"given":"Ramaswamy","family":"Kannappan","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saidulu","family":"Mattapally","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, School of Engineering, The University of Alabama at Birmingham, Birmingham, 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