小柯机器人

美国纽约纪念斯隆·凯特琳癌症中心Scott Keeney和Hajime Murakami课题组合作取得新进展。他们提出多层机制确保减数分裂中的短染色体重组。这一研究成果于2020年5月6日发表在《自然》杂志上。

他们展示了酿酒酵母如何整合多个时间上不同的途径来调节Rec114和Mer2与染色体的结合，从而控制双链断裂（DSB）感受态的持续时间。同源染色体的相互参与在前期I后期调节Rec114和Mer2的解离，而复制的时机以及与着丝粒或端粒的接近程度会影响前期I早期Rec114和Mer2的解离。

另一种早期机制增强了Rec114和Mer2结合最短染色体的“特异性”，并且承受选择压力以维持这些染色体的超重组原性。因此，生物的核型及其减数分裂错聚的风险影响其重组全貌的形状和进化。他们的结果提供了一个多方面且受进化约束的系统的整体视图，该系统将DSB分配给所有成对的同源染色体。

据介绍，在大多数物种中，同源染色体必须重组才能在减数分裂过程中准确分离。由于如果随机分布重组，小染色体将有发生错聚的风险，因此不会随意定位引发重组的DSB。尽管已知有几种途径可以调节DSB的时间、位置和数量，但如何控制DSB分布的非随机性还不清楚。减数分裂DSB由Spo11和辅助DSB蛋白（包括Rec114和Mer2）生成，它们在染色体上组装，并在真核生物中几乎普遍存在。

附：英文原文

Title: Multilayered mechanisms ensure that short chromosomes recombine in meiosis

Author: Hajime Murakami, Isabel Lam, Pei-Ching Huang, Jacquelyn Song, Megan van Overbeek, Scott Keeney

Issue&Volume: 2020-05-06

Abstract: In most species, homologous chromosomes must recombine in order to segregate accurately during meiosis1. Because small chromosomes would be at risk of missegregation if recombination were randomly distributed, the double-strand breaks (DSBs) that initiate recombination are not located arbitrarily2. How the nonrandomness of DSB distributions is controlled is not understood, although several pathways are known to regulate the timing, location and number of DSBs. Meiotic DSBs are generated by Spo11 and accessory DSB proteins, including Rec114 and Mer2, which assemble on chromosomes3,4,5,6,7 and are nearly universal in eukaryotes8,9,10,11. Here we demonstrate how Saccharomyces cerevisiae integrates multiple temporally distinct pathways to regulate the binding of Rec114 and Mer2 to chromosomes, thereby controlling the duration of a DSB-competent state. The engagement of homologous chromosomes with each other regulates the dissociation of Rec114 and Mer2 later in prophase I, whereas the timing of replication and the proximity to centromeres or telomeres influence the accumulation of Rec114 and Mer2 early in prophase I. Another early mechanism enhances the binding of Rec114 and Mer2 specifically on the shortest chromosomes, and is subject to selection pressure to maintain the hyperrecombinogenic properties of these chromosomes. Thus, the karyotype of an organism and its risk of meiotic missegregation influence the shape and evolution of its recombination landscape. Our results provide a cohesive view of a multifaceted and evolutionarily constrained system that allocates DSBs to all pairs of homologous chromosomes.

DOI: 10.1038/s41586-020-2248-2

Source: https://www.nature.com/articles/s41586-020-2248-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html