Methylations of histone H3 lysine 9 and lysine 36 are functionally linked to DNA replication checkpoint control in fission yeast

Hyun Soo Kim, Dong Keun Rhee, Yeun Kyu Jang

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23 Citations (Scopus)


Recently, histone H4 lysine 20 and H3 lysine 79 methylations were functionally linked to DNA damage checkpoint. The crosstalk between histone methylation and the S-M checkpoint, however, has remained unclear. Here, we show that H3 lysine 9 (K9) and lysine 36 (K36) methylations catalyzed by two histone methyltransferases Clr4 and Set2 are involved in hydroxyurea (HU)-induced replication checkpoint. The clr4-set2 double mutants besides histone H3-K9 and K36 double mutants exhibited HU-sensitivity, a defective HU-induced S-M checkpoint, and a significant reduction of HU-induced phosphorylation of Cdc2. Intriguingly, the clr4-set2 double mutations impaired the HU-induced accumulation of a mitotic inhibitor Mik1. Double mutants in Alp13 and Swi6, which can specifically bind to H3-K36 and K9 methylations, exhibited phenotypes similar to those of the clr4-set2 mutants. Together, these findings suggest that methylations of histone H3-K9 and K36 by Clr4 and Set2 are functionally linked to DNA replication checkpoint via accumulation of Mik1.

Original languageEnglish
Pages (from-to)419-425
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2008 Apr 4

Bibliographical note

Funding Information:
We thank Dr. Karl Ekwall for S. pombe strains. This work was supported by the Molecular and Cellular BioDiscovery Research Program (No. M10601000116-07N0100-11610) grant from the Ministry of Science and Technology, and in part by Korea Research Foundation Grant funded by Korea Government (MOEHRD, Basic Research Promotion Fund) (KRF-2005-015-C00335). In addition, this work was supported by the National Cancer Center Research Grants (0510050) to Y.K.J. and partly by 2007 Yonsei University Research Grant for New Faculty (No. 2007-1-0004) and by the Brain Korea21 (BK21) Program. D.K.R. is fellowship awardee by BK21 Program.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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