Dual recognition of phosphoserine and phosphotyrosine in histone variant H2A.X by DNA damage response protein MCPH1
Name
Singh-2012-Dual recognition of phospho-serine and phospho-tyrosine.pdf
Size
886.88 KB
Format
Adobe PDF
Checksum (MD5)
8ea35db43bd963232f25c856efcc412a
Author(s)
Singh, Namit
Basnet, Harihar
Wiltshire, Timothy D.
Mohammad, Duaa H.
Thompson, James R.
Heroux, Annie
Botuyan, Maria Victoria
Couch, Fergus J.
Rosenfeld, Michael G.
Mer, Georges
Date Issued
September 2012
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Singh, N. et al. “Dual Recognition of Phosphoserine and Phosphotyrosine in Histone Variant H2A.X by DNA Damage Response Protein MCPH1.” Proceedings of the National Academy of Sciences 109.36 (2012): 14381–14386. Web. © 2013 National Academy of Sciences.
Version
Final published version
Abstract
Tyr142, the C-terminal amino acid of histone variant H2A.X is phosphorylated by WSTF (Williams-Beuren syndrome transcription factor), a component of the WICH complex (WSTF-ISWI chromatin-remodeling complex), under basal conditions in the cell. In response to DNA double-strand breaks (DSBs), H2A.X is instantaneously phosphorylated at Ser139 by the kinases ATM and ATR and is progressively dephosphorylated at Tyr142 by the Eya1 and Eya3 tyrosine phosphatases, resulting in a temporal switch from a postulated diphosphorylated (pSer139, pTyr142) to monophosphorylated (pSer139) H2A.X state. How mediator proteins interpret these two signals remains a question of fundamental interest. We provide structural, biochemical, and cellular evidence that Microcephalin (MCPH1), an early DNA damage response protein, can read both modifications via its tandem BRCA1 C-terminal (BRCT) domains, thereby emerging as a versatile sensor of H2A.X phosphorylation marks. We show that MCPH1 recruitment to sites of DNA damage is linked to both states of H2A.X.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1212366109
