Novel characteristics of CtIP at damage-induced foci following the initiation of DNA end resection

Mutation Research
Hiroshi FujisawaHirohiko Yajima

Abstract

Homologous recombination (HR) is a major repair pathway for DNA double strand breaks (DSBs), and end resection, which generates a 3'-single strand DNA tail at the DSB, is an early step in the process. Resection is initiated by the Mre11 nuclease together with CtIP. Here, we describe novel characteristics of CtIP at DSBs. At early times following exposure of human cells to ionizing radiation, CtIP localized to the DSB, became hyperphosphorylated and formed foci in an ATM-dependent manner. At later times, when the initiation of resection had occurred, CtIP foci persist but CtIP is maintained in a hypophosphorylated state, which is dependent on ATM and ATR. Exposure to cycloheximide revealed that CtIP turns over at DSB sites downstream of resection. Our findings provide strong evidence that CtIP is continuously recruited to DSBs downstream of both the initiation and extension step of resection, strongly suggesting that CtIP has functions in addition to promoting the initiation of resection during HR.

References

Sep 16, 2005·The Journal of Biological Chemistry·Michela ClericiMaria Pia Longhese
Jul 5, 2006·Genes & Development·Xiaochun YuJunjie Chen
Oct 17, 2008·Genes & Development·Serge GravelStephen P Jackson
Oct 3, 2009·Nature Protocols·Eiji KinoshitaTohru Koike
Jan 13, 2010·Molecular Cell·Zhongsheng YouTony Hunter
Feb 15, 2011·The EMBO Journal·Atsushi ShibataPenny A Jeggo
Jan 1, 2013·Molecular Cell·Shaun E PetersonJean Gautier

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Citations

Jan 1, 2016·International Journal of Particle Therapy·Hirohiko Yajima, Lian Xue

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