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期复制，在前期压缩和重组，在中期排列。当细胞随后从中期过渡到后期时，复制的染色体被分离并分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错误，细胞仔细地调节这种中期到后期的转变，否则后期促进复合物（APC/C）（一种多聚体E3泛素连接酶）将不可逆地向前驱动这种中期到后期的转变。APC/C通过标记特异性蛋白进行蛋白水解破坏来驱动这种转变和随后的有丝分裂退出过程;它通过促进染色体凝聚蛋白的破坏来促进后期，并且它通过直接靶向细胞周期蛋白B和有丝分裂退出网络的元件来促进退出。在该项目的第一阶段，在筛选突变型C的过程中分离了几个不同APC/C基因的多个温度敏感（ts）等位基因。产生减数分裂1-细胞停滞胚胎的雌性线虫。这些等位基因的分析表明：a）APC/C是同源体和姐妹染色单体分离所必需的，B）相同的细胞周期阻滞在不同的细胞类型中可能具有不同的发育后果，和c）亚型突变体可用于检查APC/C的中期后功能。为了将这些研究扩展到包括APC/C调节剂、APC/C底物和其他后期相关的减数分裂和/或细胞类型特异性因子，本提案的具体目标是：1）研究emb-1的分子和功能特征，emb-1是不编码APC/C亚基的单中期I停滞突变体，和2）启动对具有减数分裂染色体分离和/或分离缺陷但仍发育成多细胞胚胎的新TS突变体的研究。这些研究将a）鉴定中期到后期过渡中的新的和保守的参与者，B）提供在该关键过渡期间有多少基因起作用的估计，以及c）产生能够并且将用于不同类型的减数分裂和有丝分裂细胞分裂的比较研究的ts等位基因的独特集合。

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

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

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