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酵母 IME2 在细胞周期调控的 SBF 和 MBF 靶标上游的减数分裂早期发挥作用。

Yeast IME2 functions early in meiosis upstream of cell cycle-regulated SBF and MBF targets.

机构信息

Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.

出版信息

PLoS One. 2012;7(2):e31575. doi: 10.1371/journal.pone.0031575. Epub 2012 Feb 29.

DOI:10.1371/journal.pone.0031575
PMID:22393365
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3290606/
Abstract

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 (ime2Δ), supporting an indirect role of Ime2 in Sic1 destruction. We further examined global RNA expression comparing wild type and ime2Δ 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.

摘要

背景

在酿酒酵母中,G1 周期蛋白/细胞周期蛋白依赖性激酶 (CDK) 复合物 Cln1、-2、-3/Cdk1 促进有丝分裂细胞周期中的 S 期进入,但在减数分裂中不起作用。有人提出,减数分裂特异性蛋白激酶 Ime2 是正常启动减数分裂前 DNA 复制所必需的,相当于 Cln1、-2/Cdk1。这两个 CDK 复合物在细胞周期中直接催化 B 型周期蛋白/CDK 抑制剂 Sic1 的磷酸化,使其降解。结果,Clb5、-6/Cdk1 被激活,促进 DNA 复制的起始。虽然 Ime2 在减数分裂期间 Sic1 的降解是必需的,但现在有证据表明,Ime2 并不像 Cln1、-2/Cdk1 在细胞周期中那样直接催化 Sic1 磷酸化以将其靶向失稳。

方法/主要发现:我们证明,在缺乏 IME2 基因(ime2Δ)的减数分裂细胞中,Sic1 最终降解,这支持了 Ime2 在 Sic1 降解中的间接作用。我们进一步比较了野生型和 ime2Δ细胞的全局 RNA 表达。对这些表达数据的分析提供了证据,表明 Ime2 在减数分裂早期需要正常转录许多在细胞周期 G1 晚期周期性表达的基因。

结论/意义:我们的结果将 Ime2 置于早期减数分裂途径中的一个位置,该位置位于 Cln1、-2/Cdk1 在类似细胞周期途径中占据的位置的上游。因此,Ime2 可能在促进 S 期进入方面类似于 Cln3/Cdk1,或者它在相应的减数分裂级联中甚至在上游发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/1c1eb1905ce1/pone.0031575.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/5e84bfdb93d0/pone.0031575.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/fe992e4e4728/pone.0031575.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/9a378fd8962f/pone.0031575.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/b407e0e4d6a5/pone.0031575.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/3147100b4d90/pone.0031575.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/1c1eb1905ce1/pone.0031575.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/5e84bfdb93d0/pone.0031575.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/a2804b556b6a/pone.0031575.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/fe992e4e4728/pone.0031575.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/3290606/1c1eb1905ce1/pone.0031575.g007.jpg

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