title: Novel characteristics of CtIP at damage-induced foci following the initiation of DNA end resection.
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.
authors.affiliation: School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan; Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujisawa
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimori
authors.affiliation: International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okayasu
authors.affiliation: School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Uesaka
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: hyajima@nirs.go.jp.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Yajima
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases; D006367:HeLa Cells; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D059767:Recombinational DNA Repair / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D004706:Endodeoxyribonucleases; D000076228:MRE11 Homologue Protein; C410741:RBBP8 protein, human
keywords: CtIP; DNA double strand break repair; DNA end resection; Phosphorylation