RRC ID 12590
著者 Kunoh T, Habu T, Matsumoto T.
タイトル Involvement of fission yeast Clr6-HDAC in regulation of the checkpoint kinase Cds1.
ジャーナル Nucleic Acids Res
Abstract Modification of the N-terminal tail of histones is required for various nuclear processes. Here, we show that fission yeast Clr6-HDAC (histone deacetylase) regulates the checkpoint kinase Cds1 when DNA replication encounters a stressful condition. We found that the global level of acetylation of histone H4 was constant throughout the normal cell cycle, but was reduced significantly when the cell recovered from the HU-induced cell cycle arrest (or slow DNA replication). We identified the Clr6-HDAC as a component responsible for the reduction in the level of the H4 acetylation. Although DNA replication was completed, the HU-induced cell cycle arrest could not be released even after removal of HU in the clr6-1 mutant. Under this experimental condition, Cds1 kinase was maintained active and remained bound tightly to chromatin. We also demonstrated that Cds1 was active even after treatment with caffeine, an inhibitor for ATM/ATR that is an activator of Cds1. These results indicate that inactivation of Cds1 requires functional Clr6-HDAC independently of the conventional DNA replication checkpoint. When DNA replication is impeded, Clr6-HDAC activity may monitor damage on chromatin structure/environment, which is required for inactivation of Cds1.
巻・号 36(10)
ページ 3311-9
公開日 2008-6-1
DOI 10.1093/nar/gkn203
PII gkn203
PMID 18440981
PMC PMC2425474
MeSH Acetylation Cell Cycle / drug effects Cell Cycle Proteins / metabolism* Checkpoint Kinase 2 Histone Deacetylases / metabolism* Histones / metabolism Hydroxyurea / pharmacology Protein Serine-Threonine Kinases / metabolism* Schizosaccharomyces / drug effects Schizosaccharomyces / enzymology* Schizosaccharomyces pombe Proteins / metabolism*
IF 11.502
引用数 13
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
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