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PMID: 18662539 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair.

Cell ·Vol. 134 ·No. 2 ·2008-07-25 ·Pages 231-43

Chen CC, Carson JJ, Feser J, Tamburini B, Zabaronick S, Linger J, Tyler JK

Abstract

DNA damage causes checkpoint activation leading to cell cycle arrest and repair, during which the chromatin structure is disrupted. The mechanisms whereby chromatin structure and cell cycle progression are restored after DNA repair are largely unknown. We show that chromatin reassembly following double-strand break (DSB) repair requires the histone chaperone Asf1 and that absence of Asf1 causes cell death, as cells are unable to recover from the DNA damage checkpoint. We find that Asf1 contributes toward chromatin assembly after DSB repair by promoting acetylation of free histone H3 on lysine 56 (K56) via the histone acetyl transferase Rtt109. Mimicking acetylation of K56 bypasses the requirement for Asf1 for chromatin reassembly and checkpoint recovery, whereas mutations that prevent K56 acetylation block chromatin reassembly after repair. These results indicate that restoration of the chromatin following DSB repair is driven by acetylated H3 K56 and that this is a signal for the completion of repair.

MeSH Terms
Adaptor Proteins, Signal Transducing Cell Cycle Proteins/metabolism Chromatin Assembly and Disassembly Chromatin Immunoprecipitation DNA Breaks, Double-Stranded DNA Repair DNA, Fungal/metabolism Histone Acetyltransferases/metabolism Histones/metabolism Humans Lysine/metabolism Models, Biological Molecular Chaperones Phosphoproteins/metabolism Saccharomyces cerevisiae/cytology,metabolism Saccharomyces cerevisiae Proteins/metabolism
Chemicals
ASF1 protein, S cerevisiae Adaptor Proteins, Signal Transducing Cell Cycle Proteins DNA, Fungal Histones LCD1 protein, S cerevisiae Molecular Chaperones Phosphoproteins Saccharomyces cerevisiae Proteins Histone Acetyltransferases Rtt109 protein, S cerevisiae Lysine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chen Chin-Chuan
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Carson Joshua J
Feser Jason
Tamburini Beth
Zabaronick Susan
Linger Jeffrey
Tyler Jessica K
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.06.035
Published
2008-07-25
Pages
231-43
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2610811
Subset
IM
Grants
NCI NIH HHS · R01 CA095641-06 · United States
NCI NIH HHS · R01 CA095641-03 · United States
NCI NIH HHS · R01 CA095641-05A1 · United States
NCI NIH HHS · R01 CA095641-07 · United States
NCI NIH HHS · R01 CA095641-04 · United States
NCI NIH HHS · R01 CA095641 · United States
Corrections
CommentIn
PMID: 18662534
External Links
PubMed source DOI: 10.1016/j.cell.2008.06.035 PMC Full Text View journal details
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