Involvement of fission yeast Clr6-HDAC in regulation of the checkpoint kinase Cds1

Tatsuki Kunoh, Toshiyuki Habu, Tomohiro Matsumoto

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3311-3319
Number of pages9
JournalNucleic acids research
Issue number10
Publication statusPublished - Jun 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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