Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination.
Meiosis ensures genetic diversification of gametes and sexual reproduction. For successful meiosis, multiple events such as DNA replication, recombination, and chromosome segregation must occur coordinately in a strict regulated order. We investigated the meiotic roles of Cdc7 kinase in the initiation of meiotic recombination, namely, DNA double-strand breaks (DSBs) mediated by Spo11 and other coactivating proteins. Genetic analysis using bob1-1 cdc7Delta reveals that Cdc7 is essential for meiotic DSBs and meiosis I progression. We also demonstrate that the N-terminal region of Mer2, a Spo11 ancillary protein required for DSB formation and phosphorylated by cyclin-dependent kinase (CDK), contains two types of Cdc7-dependent phosphorylation sites near the CDK site (Ser30): One (Ser29) is essential for meiotic DSB formation, and the others exhibit a cumulative effect to facilitate DSB formation. Importantly, mutations on these sites confer severe defects in DSB formation even when the CDK phosphorylation is present at Ser30. Diploids of cdc7Delta display defects in the chromatin binding of not only Spo11 but also Rec114 and Mei4, other meiotic coactivators that may assist Spo11 binding to DSB hot spots. We thus propose that Cdc7, in concert with CDK, regulates Spo11 loading to DSB sites via Mer2 phosphorylation.
Sasanuma
Hiroyuki
H
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan.
Hirota
Kouji
K
Fukuda
Tomoyuki
T
Kakusho
Naoko
N
Kugou
Kazuto
K
Kawasaki
Yasuo
Y
Shibata
Takehiko
T
Masai
Hisao
H
Ohta
Kunihiro
K
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication / Q000502:physiology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004706:Endodeoxyribonucleases; D008540:Meiosis / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011995:Recombination, Genetic / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D000099257:Meiotic Recombination Protein SPO11
D018797:Cell Cycle Proteins; D004250:DNA Topoisomerases, Type II; D004706:Endodeoxyribonucleases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; C071054:REC107 protein, S cerevisiae; C489404:CDC7 protein, S cerevisiae; C518938:Spo11 protein, S cerevisiae; D000099257:Meiotic Recombination Protein SPO11