title: Hsk1 kinase is required for induction of meiotic dsDNA breaks without involving checkpoint kinases in fission yeast.
abstract: Cdc7 kinase, conserved through evolution, is known to be essential for mitotic DNA replication. The role of Cdc7 in meiotic recombination was suggested in Saccharomyces cerevisiae, but its precise role has not been addressed. Here, we report that Hsk1, the Cdc7-related kinase in Schizosaccharomyces pombe, plays a crucial role during meiosis. In a hsk1 temperature-sensitive strain (hsk1-89), meiosis is arrested with one nucleus state before meiosis I in most of the cells and meiotic recombination frequency is reduced by one order of magnitude, whereas premeiotic DNA replication is delayed but is apparently completed. Strikingly, formation of meiotic dsDNA breaks (DSBs) are largely impaired in the mutant, and Hsk1 kinase activity is essential for these processes. Deletion of all three checkpoint kinases, namely Cds1, Chk1, and Mek1, does not restore DSB formation, meiosis, or Cdc2 activation, which is suppressed in hsk1-89, suggesting that these aberrations are not caused by known checkpoint pathways but that Hsk1 may regulate DSB formation and meiosis. Whereas transcriptional induction of some rec genes and horsetail movement are normal, chromatin remodeling at ade6-M26, a recombination hotspot, which is prerequisite for subsequent DSB formation at this locus, is not observed in hsk1-89. These results indicate unique and essential roles of Hsk1 kinase in the initiation of meiotic recombination and meiosis.
authors.affiliation: Genome Dynamics Project and Department of Integrated Life Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ogino
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirota
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Takeda
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ohta
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Arai
authors.forename: Hisao
authors.initials: H
authors.lastname: Masai
mesh_terms: D001973:Bromodeoxyuridine / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000502:physiology*; D002843:Chromatin / Q000737:chemistry; D004249:DNA Damage; D008540:Meiosis; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011995:Recombination, Genetic; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000502:physiology*; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D029702:Schizosaccharomyces pombe Proteins; C068619:CDC7 protein, human; C094761:HSK1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D001973:Bromodeoxyuridine