| Yeast G1 DNA damage checkpoint regulation by H2A phosphorylation is independent of chromatin remodeling. | |
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MedLine Citation:
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PMID: 16940359 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent studies of yeast G1 DNA damage response have identified characteristic changes in chromatin adjacent to double-strand breaks (DSBs). Histone H2A (yeast H2AX) is rapidly phosphorylated on S129 by the kinase Tel1 (ATM) over a domain extending kilobases from the DSB. The adaptor protein Rad9 (53BP1) is recruited to this chromatin domain through binding of its tudor domains to histone H3 diMe-K79. Multisite phosphorylation of Rad9 by Mec1 (ATR) then activates the signaling kinase Rad53 (CHK2) to induce a delay in G1. Here, we report a previously undescribed role for Tel1 in G1 checkpoint response and show that H2A is the likely phosphorylation target, in a much as S129 mutation to Ala confers defects in G1 checkpoint arrest, Rad9 phosphorylation, and Rad53 activation. Importantly, Rad9 fails to bind chromatin adjacent to DSBs in H2A-S129A mutants. Previous work showed that H2A phosphorylation allows binding of NuA4, SWR, and INO80 chromatin remodeling complexes, perhaps exposing H3 diMe-K79. Yet, mutants lacking SWR or INO80 remain checkpoint competent, whereas loss of NuA4-dependent histone acetylation leads to G1 checkpoint persistence, suggesting that H2A phosphorylation promotes two independent events, rapid Rad9 recruitment to DSBs and subsequent remodeling by NuA4, SWR, and INO80. |
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Authors:
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Ali Javaheri; Robert Wysocki; Olivier Jobin-Robitaille; Mohammed Altaf; Jacques Côté; Stephen J Kron |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-08-29 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 103 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-09-13 Completed Date: 2006-10-30 Revised Date: 2013-06-07 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 13771-6 Citation Subset: IM |
Affiliation:
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Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetyltransferases
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metabolism Cell Cycle Proteins / metabolism Chromatin Assembly and Disassembly / genetics DNA Damage* Fungal Proteins / genetics, physiology* G1 Phase / genetics* Histone Acetyltransferases Histones / metabolism* Intracellular Signaling Peptides and Proteins Mutation Phosphorylation Protein-Serine-Threonine Kinases / metabolism Saccharomyces cerevisiae / genetics, metabolism* Saccharomyces cerevisiae Proteins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM60443/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Fungal Proteins; 0/Histones; 0/INO80 complex, S cerevisiae; 0/Intracellular Signaling Peptides and Proteins; 0/Saccharomyces cerevisiae Proteins; 139691-42-2/rad9 protein; EC 2.3.1.-/Acetyltransferases; EC 2.3.1.48/Histone Acetyltransferases; EC 2.3.1.48/NuA4 protein, S cerevisiae; EC 2.7.1.-/RAD53 protein, S cerevisiae; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/TEL1 protein, S cerevisiae |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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