Sic1-induced DNA rereplication during meiosis.
Orderly progression through meiosis requires strict regulation of DNA metabolic events, so that a single round of DNA replication is systematically followed by a recombination phase and 2 rounds of chromosome segregation. We report here the disruption of this sequence of events in Saccharomyces cerevisiae through meiosis-specific induction of the cyclin-dependent kinase (CDK) inhibitor Sic1 mutated at multiple phosphorylation sites. Accumulation of this stabilized version of Sic1 led to significant DNA rereplication in the absence of normal chromosome segregation. Deletion of DMC1 abolished DNA rereplication, but additional deletion of RAD17 restored the original phenotype. Therefore, activation of the meiotic recombination checkpoint, which arrests meiotic progression at pachytene, suppressed DNA rereplication resulting from Sic1 stabilization. In contrast to deletion of DMC1, deletion of NDT80, which encodes a transcription factor required for pachytene exit, did not inhibit DNA rereplication. Our results provide strong evidence that CDK activity is required to prevent inappropriate initiation of DNA synthesis before the meiotic divisions.
Sawarynski
Kara E
KE
Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Najor
Nicole A
NA
Kepsel
Andrea C
AC
Brush
George S
GS
D017489:CDC28 Protein Kinase, S cerevisiae / Q000037:antagonists & inhibitors / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology*; D020090:Chromosome Segregation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology; D008540:Meiosis; D009154:Mutation; D049471:Pachytene Stage; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000166:cytology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C513033:DMC1 protein, S cerevisiae; D004268:DNA-Binding Proteins; C097071:NDT80 protein, S cerevisiae; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D017489:CDC28 Protein Kinase, S cerevisiae