Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

doi:10.1016/J.BBRC.2014.09.038

Title: Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

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Abstract

Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after 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:

Du, Fengxia ^[1]; Zhang, Minjie ^[1]; Li, Xiaohua; Yang, Caiyun ^[1]; Meng, Hao; Wang, Dong; Chang, Shuang ^[1]; Xu, Ye ^[2]; Price, Brendan ^[2]; Sun, Yingli ^[1]

Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China)
Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134 (United States)

Publication Date:: Fri Oct 03 00:00:00 EDT 2014

OSTI Identifier:: 22416774

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 452; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; DIMERS; DISSOCIATION; DNA REPAIR; IRRADIATION; MONOMERS; PHOSPHORYLATION; PROTEINS; SERINE; STRAND BREAKS; SUBSTRATES; THREONINE

Citation Formats


                    Du, Fengxia, Zhang, Minjie, University of Chinese Academy of Sciences, Beijing 100049, Li, Xiaohua, Yang, Caiyun, Meng, Hao, Wang, Dong, Chang, Shuang, University of Chinese Academy of Sciences, Beijing 100049, Xu, Ye, Price, Brendan, and Sun, Yingli. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair.  United States: N. p., 2014. 
        Web.  doi:10.1016/J.BBRC.2014.09.038.

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                    Du, Fengxia, Zhang, Minjie, University of Chinese Academy of Sciences, Beijing 100049, Li, Xiaohua, Yang, Caiyun, Meng, Hao, Wang, Dong, Chang, Shuang, University of Chinese Academy of Sciences, Beijing 100049, Xu, Ye, Price, Brendan, & Sun, Yingli. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair.  United States.  https://doi.org/10.1016/J.BBRC.2014.09.038

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                    Du, Fengxia, Zhang, Minjie, University of Chinese Academy of Sciences, Beijing 100049, Li, Xiaohua, Yang, Caiyun, Meng, Hao, Wang, Dong, Chang, Shuang, University of Chinese Academy of Sciences, Beijing 100049, Xu, Ye, Price, Brendan, and Sun, Yingli. 2014.  
        "Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair".  United States.  https://doi.org/10.1016/J.BBRC.2014.09.038.

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@article{osti_22416774,

  title        = {Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair},

  author       = {Du, Fengxia and Zhang, Minjie and University of Chinese Academy of Sciences, Beijing 100049 and Li, Xiaohua and Yang, Caiyun and Meng, Hao and Wang, Dong and Chang, Shuang and University of Chinese Academy of Sciences, Beijing 100049 and Xu, Ye and Price, Brendan and Sun, Yingli},

  abstractNote = {Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after 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.},

  doi          = {10.1016/J.BBRC.2014.09.038},

  url          = {https://www.osti.gov/biblio/22416774},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 4,

  volume       = 452,

  place        = {United States},

  year         = {Fri Oct 03 00:00:00 EDT 2014},

  month        = {Fri Oct 03 00:00:00 EDT 2014}

}

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