美国斯隆—凯特林癌症研究所Scott Keeney、Maria Jasin、Laurent Acquaviva等研究人员合作发现,小鼠假常染色体区域会形成减数分裂DNA的断裂。这一研究成果于2020年5月27日在线发表在《自然》上。
Title: Ensuring meiotic DNA break formation in the mouse pseudoautosomal region
Author: Laurent Acquaviva, Michiel Boekhout, Mehmet E. Karasu, Kevin Brick, Florencia Pratto, Tao Li, Megan van Overbeek, Liisa Kauppi, R. Daniel Camerini-Otero, Maria Jasin, Scott Keeney
Issue&Volume: 2020-05-27
Abstract: Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation1,2. How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis.
DOI: 10.1038/s41586-020-2327-4
Source: https://www.nature.com/articles/s41586-020-2327-4
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
本期文章:《自然》:Online/在线发表