Premium
Dynamic chromatin modifications during repair of DNA double strand breaks
Author(s) -
Cote Jacques,
Allard Stéphane,
JobinRobitaille Olivier,
Fortin Israël,
Auger Andréanne,
Lacoste Nicolas,
Utley Rhea T,
Bouchard Nathalie,
Covic Marcela,
Altaf Mohd
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a889-b
Subject(s) - chromatin , microbiology and biotechnology , biology , histone h2a , chromatin remodeling , histone , histone code , dna repair , histone acetyltransferase , genetics , dna , nucleosome
The NuA4 histone acetyltransferase is a highly conserved multisubunit complex responsible for acetylation of nucleosomal histone H4 and H2A. Mutations in different NuA4 subunits create cell cycle arrest or delay in G2/M. The NuA4 complex is important for the efficient repair of DNA double strand breaks (DSBs) in vivo. NuA4 is rapidly recruited on chromatin surrounding a DSB in vivo at the same time histone H2A is phosphorylated at serine 129 in the neighboring region. This modification is functionally equivalent to the phosphorylation of H2AX Ser139 in mammals. ATP‐dependent chromatin remodeling complex Ino80 and the Rvb1 helicase are also recruited upon formation of a DSB in vivo but are delayed compared to NuA4. Prior chromatin acetylation by NuA4 is required for efficient Ino80/Rvb1 binding. Furthermore, NuA4 dependent acetylation of chromatin around a DSB is lost 2–4 hrs after break formation, at the same time we detect local phosphorylation of histone H4 at serine 1 by CKII. This mark blocks reacetylation by the NuA4 complex and could be linked to restoration of chromatin after repair/adaptation. In addition, we found that NuA4 is phosphorylated in response to DNA damage and its recruitment to the DSB is regulated during the cell cycle. Finally, NuA4 role in DNA repair is functionally linked to Rad9 signaling and Dot1‐dependent methylation of histone H3. Local regulation of NuA4 activity/retention by specific sequential histone phosphorylation events and stepwise action of chromatin modifiers/remodelers are certainly important mechanisms used by the cell to allow efficient DNA repair and the maintenance of genome integrity. This work is supported by a grant from the Canadian Institutes of Health Research.