Yeast IME2 Functions Early in Meiosis Upstream of Cell Cycle-Regulated SBF and MBF Targets

被引:8
作者
Brush, George S. [1 ,2 ,3 ,4 ]
Najor, Nicole A. [4 ]
Dombkowski, Alan A. [5 ]
Cukovic, Daniela [5 ]
Sawarynski, Kara E. [3 ]
机构
[1] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA
[2] Barbara Ann Karmanos Canc Inst, Program Mol Biol & Genet, Detroit, MI USA
[3] Wayne State Univ, Sch Med, Canc Biol Grad Program, Detroit, MI USA
[4] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA
[5] Wayne State Univ, Sch Med, Dept Pediat, Childrens Hosp Michigan,Div Clin Pharmacol & Toxi, Detroit, MI 48201 USA
基金
美国国家卫生研究院;
关键词
SACCHAROMYCES-CEREVISIAE; S-PHASE; DNA-REPLICATION; PROTEIN-KINASE; BUDDING YEAST; G1-SPECIFIC TRANSCRIPTION; GENE-EXPRESSION; G1; CYCLINS; PHOSPHORYLATION; INHIBITOR;
D O I
10.1371/journal.pone.0031575
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: In Saccharomyces cerevisiae, the G1 cyclin/cyclin-dependent kinase (CDK) complexes Cln1,-2,-3/Cdk1 promote S phase entry during the mitotic cell cycle but do not function during meiosis. It has been proposed that the meiosis-specific protein kinase Ime2, which is required for normal timing of pre-meiotic DNA replication, is equivalent to Cln1,-2/Cdk1. These two CDK complexes directly catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic1 during the cell cycle to enable its destruction. As a result, Clb5,-6/Cdk1 become activated and facilitate initiation of DNA replication. While Ime2 is required for Sic1 destruction during meiosis, evidence now suggests that Ime2 does not directly catalyze Sic1 phosphorylation to target it for destabilization as Cln1,-2/Cdk1 do during the cell cycle. Methodology/Principal Findings: We demonstrated that Sic1 is eventually degraded in meiotic cells lacking the IME2 gene (ime2 Delta), supporting an indirect role of Ime2 in Sic1 destruction. We further examined global RNA expression comparing wild type and ime2D cells. Analysis of these expression data has provided evidence that Ime2 is required early in meiosis for normal transcription of many genes that are also periodically expressed during late G1 of the cell cycle. Conclusions/Significance: Our results place Ime2 at a position in the early meiotic pathway that lies upstream of the position occupied by Cln1,-2/Cdk1 in the analogous cell cycle pathway. Thus, Ime2 may functionally resemble Cln3/Cdk1 in promoting S phase entry, or it could play a role even further upstream in the corresponding meiotic cascade.
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页数:12
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