title: Methylations of histone H3 lysine 9 and lysine 36 are functionally linked to DNA replication checkpoint control in fission yeast.
abstract: 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.
authors.affiliation: Research Institute, National Cancer Center, Goyang, Gyeonggi 411-769, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Dong Keun
authors.initials: DK
authors.lastname: Rhee
authors.forename: Yeun Kyu
authors.initials: YK
authors.lastname: Jang
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D019175:DNA Methylation; D004261:DNA Replication / Q000502:physiology*; D018816:Genes, cdc / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology* / Q000502:physiology*
chemical_list: D006657:Histones; D008239:Lysine