TY - JOUR
T1 - Involvement of fission yeast Clr6-HDAC in regulation of the checkpoint kinase Cds1
AU - Kunoh, Tatsuki
AU - Habu, Toshiyuki
AU - Matsumoto, Tomohiro
N1 - Funding Information:
We thank O. Niwa, J. Nakayama, T. Shimura and all members of Radiation Biology Center for reagents, procedures and helpful discussions. We are particularly grateful to M. Yanagida, C. Shimoda, I. M. Hagan, K. Ekwall, R. C. Allshire, A. Baines and E. Sonoda for strains, plasmids, antibodies and procedures. This work was supported by the 21st Century COE grant from the Ministry of Education, Sports, Culture, and Technology, Japan to T.M. T.K. was partly supported by a grant to O. Niwa from Nuclear Safety Research Association, Tokyo.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkn203
DO - 10.1093/nar/gkn203
M3 - Article
C2 - 18440981
AN - SCOPUS:45549093388
VL - 36
SP - 3311
EP - 3319
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 10
ER -