Metaphase to Anaphase Transition in Mitosis and Meiosis

有丝分裂和减数分裂的中期到后期的转变

• 批准号: 6668840
• 负责人: DIANE CAROL SHAKES
• 金额: $ 14.31万
• 依托单位: COLLEGE OF WILLIAM AND MARY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668840
• 关键词: Caenorhabditis elegans; cell cycle; cell cycle proteins; chromosome movement; cyclins; cytogenetics; developmental genetics; enzyme complex; enzyme substrate complex; genetic crossing over; ligase; meiosis; mutant; protein degradation; ubiquitin

DESCRIPTION (provided by applicant): During the normal process of eukaryotic cell division, chromosomes are replicated during S-phase, compacted and restructured during prophase, and aligned during metaphase. As cells subsequently transition from metaphase-to-anaphase, the replicated chromosomes are separated and segregated to each of two daughter cells. To avoid lethal errors in chromosome segregation, cells carefully regulate this metaphase to anaphase transition which would otherwise be driven irreversibly forward by the anaphase-promoting complex (APC/C), a multimeric E3 ubiquitin ligase. The APC/C drives both this transition and the subsequent process of mitotic exit by tagging specific proteins for proteolytic destruction; it promotes anaphase by facilitating the destruction of chromosomal cohesion proteins, and it promotes exit by directly targeting cyclin B and elements of the mitotic exit network. In the first phase of this project, multiple temperature-sensitive (ts) alleles of several different APC/C genes were isolated in screens for mutant C. elegans mothers that produce meiotic 1-cell arrested embryos. Analysis of these alleles revealed that: a) the APC/C is required for homolog as well as sister chromatid separation, b) identical cell cycle blocks can have distinct developmental consequence in different cell types, and c) hypomorphic mutants can be used to examine the post-metaphase functions of the APC/C. With the goal of extending these studies to include APC/C regulators, APC/C substrates, and other anaphase-related meiotic and/or cell type specific factors, the specific aims of this proposal are: 1) to pursue the molecular and functional characterization of emb-1, the single metaphase I arrested mutant that does not encode an APC/C subunit, and 2) to initiate studies of new ts mutants with defects in meiotic chromosome separation and/or segregation which nevertheless develop into multi-cellular embryos. These studies will a) identify novel and conserved players in the metaphase-to-anaphase transition, b) provide an estimate of how many genes function during this critical transition, and c) generate a unique collection of ts alleles that can and will be used in comparative studies of different types of meiotic and mitotic cell divisions.

描述（由申请人提供）：在真核细胞分裂的正常过程中，染色体在S期间重复，在预言期间进行压缩和重组，并在中期期间对齐。随后细胞从中期到分子过渡，将复制的染色体分离并隔离到两个子细胞中的每一个。为了避免染色体分离中的致命误差，细胞仔细调节了该中期向后期转变，否则该中期将由多聚体E3泛素连接酶（APC/C）不可逆地向前驱动。 APC/C通过标记特定蛋白质以促进蛋白水解破坏，驱动了这种过渡和随后的有丝分裂退出过程。它通过促进染色体内聚蛋白的破坏来促进后期，并通过直接靶向细胞周期蛋白B和有丝分裂出口网络的元素来促进退出。在该项目的第一阶段中，在筛选中，在筛选中分离了几个不同的APC/C基因的多个温度敏感（TS）等位基因，用于突变的秀丽隐杆线虫母亲，产生减数分裂1细胞阻止的胚胎。对这些等位基因的分析表明：a）APC/C是同源物以及姐妹染色单体分离所必需的，b）相同的细胞周期块可以在不同的细胞类型中具有明显的发育后果，并且c）可用于检查APC/C的米型后运动酶功能。将这些研究扩展到包括APC/C调节剂，APC/C底物以及其他与后期相关的减数分裂和/或细胞类型的特定因素的目的，该提议的具体目的是：1）追求Emb-1的分子和功能表征的分子和功能性特征，该突变与APC/C cutunit的无限制突变和2）intect in New to new to new of Apc/c Subunit和2）染色体分离和/或隔离，但发展为多细胞胚胎。这些研究将a）在中期到时代的转变中识别新颖和保守的参与者，b）提供估计该临界过渡过程中有多少基因功能的估计，c）产生了独特的TS等位基因集合，可以并且将用于对不同类型的减素和有丝分裂细胞划分的比较研究。

项目成果

Multiple subunits of the Caenorhabditis elegans anaphase-promoting complex are required for chromosome segregation during meiosis I.

减数分裂 I 期间的染色体分离需要秀丽隐杆线虫后期促进复合体的多个亚基。

• DOI: 10.1093/genetics/160.2.805
• 发表时间: 2002
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Davis,EdwardS;Wille,Lucia;Chestnut,BarryA;Sadler,PennyL;Shakes,DianeC;Golden,Andy
• 通讯作者: Golden,Andy

Developmental defects observed in hypomorphic anaphase-promoting complex mutants are linked to cell cycle abnormalities.

在低效性后期促进复合体突变体中观察到的发育缺陷与细胞周期异常有关。

• DOI: 10.1242/dev.00385
• 发表时间: 2003
• 期刊: Development (Cambridge, England)
• 作者: Shakes,DianeC;Sadler,PennyL;Schumacher,JillM;Abdolrasulnia,Maziar;Golden,Andy
• 通讯作者: Golden,Andy

emb-1 encodes the APC16 subunit of the Caenorhabditis elegans anaphase-promoting complex.

• DOI: 10.1534/genetics.111.131714
• 发表时间: 2011-10
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Shakes DC;Allen AK;Albert KM;Golden A
• 通讯作者: Golden A

Asymmetric spermatocyte division as a mechanism for controlling sex ratios.

• DOI: 10.1038/ncomms1160
• 发表时间: 2011-01-18
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Shakes DC;Neva BJ;Huynh H;Chaudhuri J;Pires-Dasilva A
• 通讯作者: Pires-Dasilva A