collaborative action of brca1 and ctip in elimination of covalent modifications from double-strand breaks to facilitate subsequent break repair合作行动的brca1和ctip消除共价修饰的双链断裂,以方便后续修复.pdfVIP

Collaborative Action of Brca1 and CtIP in Elimination of Covalent Modifications from Double-Strand Breaks to Facilitate Subsequent Break Repair 1 1 2 2 1 Kyoko Nakamura , Toshiaki Kogame , Hiroyuki Oshiumi , Akira Shinohara , Yoshiki Sumitomo , Keli 3 3 4 4 5 6 Agama , Yves Pommier , Kimiko M. Tsutsui , Ken Tsutsui , Edgar Hartsuiker , Tomoo Ogi , Shunichi 1 1 Takeda , Yoshihito Taniguchi * 1 Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2 Institute for Protein Research, Graduate School of Science, Osaka University, Suita, Osaka, Japan, 3 Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 4 Department of Neurogenomics, Department of Genome Dynamics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan, 5 Cancer Biology, North West Cancer Research Fund Institute, Bangor University, Bangor, United Kingdom, 6 Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan Abstract Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks (DSBs) in genomic DNA in cycling cells. These DSBs are often covalently bound with polypeptides at the 39 and 59 ends. Such modifications must be eliminated before DSB repair can take place, but it remains elusive which nucleases are involved in this process. Previous studies show that CtIP plays a critical role in the generation of 39 single-strand overhang at ‘‘