title: Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair.
abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Du
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Meng
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134, USA. Electronic address: Brendan_Price@dfci.harvard.edu.
authors.forename: Brendan
authors.initials: B
authors.lastname: Price
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: sunyl@big.ac.cn.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Sun
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D002460:Cell Line; D004260:DNA Repair / Q000502:physiology*; D019281:Dimerization; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D044367:Phase Transition; D010766:Phosphorylation
chemical_list: C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM activation; DNA repair; Dephosphorylation; Intermolecular phosphorylation