@article{31e57171852c44b8a056f0b529af71f7,
title = "CtIP Links DNA Double-Strand Break Sensing to Resection",
abstract = "In response to DNA double-strand breaks (DSBs), cells sense the DNA lesions and then activate the protein kinase ATM. Subsequent DSB resection produces RPA-coated ssDNA that is essential for activation of the DNA damage checkpoint and DNA repair by homologous recombination (HR). However, the biochemical mechanism underlying the transition from DSB sensing to resection remains unclear. Using Xenopus egg extracts and human cells, we show that the tumor suppressor protein CtIP plays a critical role in this transition. We find that CtIP translocates to DSBs, a process dependent on the DSB sensor complex Mre11-Rad50-NBS1, the kinase activity of ATM, and a direct DNA-binding motif in CtIP, and then promotes DSB resection. Thus, CtIP facilitates the transition from DSB sensing to processing: it does so by binding to the DNA at DSBs after DSB sensing and ATM activation and then promoting DNA resection, leading to checkpoint activation and HR.",
keywords = "DNA, PROTEINS",
author = "Zhongsheng You and Shi, \{Linda Z.\} and Quan Zhu and Peng Wu and Zhang, \{You Wei\} and Andrew Basilio and Nina Tonnu and Verma, \{Inder M.\} and Berns, \{Michael W.\} and Tony Hunter",
note = "Funding Information: We thank Matthew Weitzman, Paul Russell, Walter Eckhart, Douglass Forbes, Helen Piwnica-Worms, Julie Bailis, Nicole Orazio, and Charly Chahwan for critical discussions and Jill Meisenhelder, Suzy Simon, Justin Zimmermann, and David Chambers for technical support. We thank Jeremy Copp and Gerald Pao for providing Xenopus and human CtIP cDNA and Graeme Smith and Mark O'Connor for providing the ATM inhibitor KU-55933. T.H. is a Frank and Else Schilling American Cancer Society Research Professor. M.W.B. is the Arnold and Mabel Beckman Professor at UC Irvine and Adjunct Professor of Bioengineering at UC San Diego. I.M.V. is an American Cancer Society Professor of Molecular Biology. This work was supported by a grant from the American Cancer Society (IRG-58-010-52 to Z.Y.), by US Public Health Service Grants CA14195 and CA80100 from the NCI (T.H.), by grants from the Air Force Office of Scientific Research (F9620-00-1-0371) and the Beckman Laser Institute Foundation (M.W.B.), and by grants from the NIH, Leducq Foundation, Lustgarten Foundation, Ellison Medical Foundation, and the H.N. and Frances C. Berger Foundation (I.M.V.). ",
year = "2009",
month = dec,
day = "24",
doi = "10.1016/j.molcel.2009.12.002",
language = "English",
volume = "36",
pages = "954--969",
journal = "Molecular cell",
issn = "1097-2765",
number = "6",
}