RRC ID 17586
著者 Tougan T, Kasama T, Ohtaka A, Okuzaki D, Saito TT, Russell P, Nojima H.
タイトル The Mek1 phosphorylation cascade plays a role in meiotic recombination of Schizosaccharomyces pombe.
ジャーナル Cell Cycle
Abstract Mek1 is a Chk2/Rad53/Cds1-related protein kinase that is required for proper meiotic progression of Schizosaccharomyces pombe. However, the molecular mechanisms of Mek1 regulation and Mek1 phosphorylation targets are unclear. Here, we report that Mek1 is phosphorylated at serine-12 (S12), S14 and threonine-15 (T15) by Rad3 (ATR) and/or Tel1 (ATM) kinases that are activated by meiotic programmed double-strand breaks (DSBs). Mutations of these sites by alanine replacement caused abnormal meiotic progression and recombination rates. Phosphorylation of these sites triggers autophosphorylation of Mek1; indeed, alanine replacement mutations of Mek1-T318 and -T322 residues in the activation loop of Mek1 reduced Mek1 kinase activity and meiotic recombination rates. Substrates of Mek1 include Mus81-T275, Rdh54-T6 and Rdh54-T673. Mus81-T275 is known to regulate the Mus81 function in DNA cleavage, whereas Rdh54-T6A/T673A mutant cells showed abnormal meiotic recombination. Taken together, we conclude that the phosphorylation of Mek1 by Rad3 or Tel1, Mek1 autophosphorylation and Mus81 or Rdh54 phosphorylation by Mek1 regulate meiotic progression in S. pombe.
巻・号 9(23)
ページ 4688-702
公開日 2010-12-1
DOI 10.4161/cc.9.23.14050
PII 14050
PMID 21084840
PMC PMC3048037
MeSH Amino Acid Sequence Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Cycle Proteins / physiology Checkpoint Kinase 2 DNA Breaks, Double-Stranded DNA-Binding Proteins / metabolism Endonucleases / metabolism MAP Kinase Kinase 1 / genetics MAP Kinase Kinase 1 / metabolism* MAP Kinase Kinase 1 / physiology Meiosis* Molecular Sequence Data Mutation Phosphorylation Protein Kinases / metabolism Protein Serine-Threonine Kinases / metabolism Recombination, Genetic Schizosaccharomyces / enzymology* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Schizosaccharomyces pombe Proteins / physiology
IF 3.699
引用数 6
WOS 分野 CELL BIOLOGY
リソース情報
酵母 CD16-1, TP4-5A, TP4-1D, JZ670