PTIP promotes DNA double-strand break repair through homologous recombination.
PTIP (Pax2 transactivation domain-interacting protein) is a large nuclear protein containing six BRCT (BRCA1 C-Terminal) domains. PTIP is recruited to DNA-damage sites through its BRCT domains and thus has been implicated in the DNA damage response. To define the function of PTIP in DNA repair, we disrupted the PTIP gene of the chicken DT40 B cell line. PTIP mutant (PTIP(-/-/-) ) cells displayed phenotypes frequently observed in cells with defective homologous recombination (HR), i.e. a marked increase in the number of spontaneously arising DNA lesions as well as sensitivity to ionizing radiation (IR) and the topoisomerase I inhibitor, camptothecin. Accordingly, analysis of HR efficiency by using artificial recombination substrates showed that the HR efficiency was reduced in the PTIP-deficient chicken and the PTIP-depleted HeLa cells. As microarray analysis showed no apparent difference between wild-type and PTIP(-/-/-) cells in the expression of known HR factors, it is unlikely that this reduction in HR efficiency in PTIP-deficient cells is associated with PTIP's role in transcriptional regulation. We thus propose that PTIP promotes double-strand break repair through a direct role in HR.
Wang
Xin
X
Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan.
Takenaka
Katsuya
K
Takeda
Shunichi
S
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002166:Camptothecin / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002645:Chickens; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins; D054659:Diketopiperazines; D055785:Gene Knockdown Techniques; D042822:Genomic Instability; D006367:HeLa Cells; D059765:Homologous Recombination; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D059003:Topoisomerase Inhibitors / Q000494:pharmacology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D054659:Diketopiperazines; D009687:Nuclear Proteins; C485876:PAXIP1 protein, human; D010879:Piperazines; D059003:Topoisomerase Inhibitors; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D002166:Camptothecin