A brief historical perspective on cell cycle control of CENP-A assembly and inheritance.

IF 2.8 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Grant Rowley, Lars E T Jansen
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Abstract

Centromeres provide the chromosomal scaffold for the assembly of the kinetochore complex, thereby linking replicated sister chromatids to the mitotic spindle, driving their segregation into nascent daughter cells. The location and maintenance of centromeres rely, in large part, on a unique conserved chromatin domain, defined by nucleosomes containing the histone H3 variant, Centromere Protein A (CENP-A), whose discovery 40 years ago we now celebrate. Current models place CENP-A, along with many of its orthologs, at the centre of a self-propagating epigenetic feedback loop that heritably maintains centromere position through mitotic and meiotic divisions. CENP-A is stably recycled through DNA replication but requires replenishment each cell cycle. In many organisms, assembly is restricted to G1 phase, indicating tight cell cycle control of the assembly machinery. Here, we provide a historical overview of the discoveries that led to current models of cell cycle control of centromere assembly, starting with early models of regulation to the intricate, multi-layered phosphoregulation revealed to date. Our review focuses primarily on the human and other animal systems, in which the current view is that negative and positive control through cyclin-dependent kinases and Polo-like kinase 1 combine to link CENP-A assembly to mitotic exit. Cell cycle-coupled CENP-A assembly has been attributed to so-called licensing or priming events. We discuss the validity of these models and terminology and highlight key outstanding questions that remain unanswered.

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细胞周期控制的简史回顾:CENP-A组装和遗传。
着丝粒为着丝点复合体的组装提供染色体支架,从而将复制的姐妹染色单体与有丝分裂纺锤体连接起来,推动它们分离成新生的子细胞。着丝粒的定位和维持在很大程度上依赖于一个独特的保守的染色质结构域,该结构域由核小体定义,核小体含有组蛋白H3变体,着丝粒蛋白a (CENP-A),它在40年前被发现,我们现在庆祝。目前的模型将CENP-A及其许多同源基因置于自我繁殖的表观遗传反馈回路的中心,该回路通过有丝分裂和减数分裂遗传地维持着丝粒位置。CENP-A通过DNA复制稳定地循环,但每个细胞周期都需要补充。在许多生物体中,装配仅限于G1期,这表明装配机制受到细胞周期的严格控制。在这里,我们提供了导致着丝粒组装的细胞周期控制当前模型的发现的历史概述,从迄今为止揭示的复杂的多层磷酸化调控的早期模型开始。我们的综述主要集中在人类和其他动物系统,目前的观点是,通过周期蛋白依赖激酶和polo样激酶1的阴性和阳性控制,将CENP-A组装与有丝分裂退出联系起来。细胞周期偶联的CENP-A组装被归因于所谓的许可或启动事件。我们将讨论这些模型和术语的有效性,并强调仍未解决的关键突出问题。
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来源期刊
Chromosome Research
Chromosome Research 生物-生化与分子生物学
CiteScore
4.70
自引率
3.80%
发文量
31
审稿时长
1 months
期刊介绍: Chromosome Research publishes manuscripts from work based on all organisms and encourages submissions in the following areas including, but not limited, to: · Chromosomes and their linkage to diseases; · Chromosome organization within the nucleus; · Chromatin biology (transcription, non-coding RNA, etc); · Chromosome structure, function and mechanics; · Chromosome and DNA repair; · Epigenetic chromosomal functions (centromeres, telomeres, replication, imprinting, dosage compensation, sex determination, chromosome remodeling); · Architectural/epigenomic organization of the genome; · Functional annotation of the genome; · Functional and comparative genomics in plants and animals; · Karyology studies that help resolve difficult taxonomic problems or that provide clues to fundamental mechanisms of genome and karyotype evolution in plants and animals; · Mitosis and Meiosis; · Cancer cytogenomics.
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