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Spo11的协同切割阐明减数分裂的DNA断裂机制
2021-06-13 15:09

英国苏塞克斯大学Matthew J. Neale、Valerie Garcia等研究人员合作发现,Spo11的协同切割阐明减数分裂的DNA断裂机制。这一研究成果于2021年6月9日在线发表在国际学术期刊《自然》上。

研究人员表示,遗传重组在减数分裂期间通过修复由Spo11(一种拓扑异构酶样蛋白 )产生的DNA双链断裂(DSB)而产生。Spo11 DSB优先在被称为热点的核小体耗尽区域中形成,但人们对Spo11如何与其DNA底物结合来催化DNA切割知之甚少。

尽管大多数重组事件是由单个Spo11切割引发的,但研究人员在酿酒酵母中展示了超定位的、由33到100多个碱基对分隔的协同Spo11 DSB,被称之为“双切割”。值得注意的是,双切割的长度以10.5个碱基对的周期变化,这在酵母和小鼠中是保守的。这一发现揭示了一种模型:相邻Spo11分子的方向相对于DNA螺旋是固定的——这得到了Spo11核心复合物的体外DNA结合特性的支持。减数分裂后代的深度测序确定了重组疤痕,这与由相邻Spo11 DSB产生的修复一致。总的来说,这些结果修改了人们目前对Spo11-DSB形成机制的理解,并扩展了减数分裂期间间隙修复的原始概念,并包括由Spo11本身产生的DNA间隙。 

附:英文原文

Title: Concerted cutting by Spo11 illuminates meiotic DNA break mechanics

Author: Dominic Johnson, Margaret Crawford, Tim Cooper, Corentin Claeys Bouuaert, Scott Keeney, Bertrand Llorente, Valerie Garcia, Matthew J. Neale

Issue&Volume: 2021-06-09

Abstract: Genetic recombination arises during meiosis through the repair of DNA double-strand breaks (DSBs) that are created by Spo11, a topoisomerase-like protein1,2. Spo11 DSBs form preferentially in nucleosome-depleted regions termed hotspots3,4, yet how Spo11 engages with its DNA substrate to catalyse DNA cleavage is poorly understood. Although most recombination events are initiated by a single Spo11 cut, here we show in Saccharomyces cerevisiae that hyperlocalized, concerted Spo11 DSBs separated by 33 to more than 100 base pairs also form, which we term ‘double cuts’. Notably, the lengths of double cuts vary with a periodicity of 10.5 base pairs, which is conserved in yeast and mice. This finding suggests a model in which the orientation of adjacent Spo11 molecules is fixed relative to the DNA helix—a proposal supported by the in vitro DNA-binding properties of the Spo11 core complex. Deep sequencing of meiotic progeny identifies recombination scars that are consistent with repair initiated from gaps generated by adjacent Spo11 DSBs. Collectively, these results revise our present understanding of the mechanics of Spo11-DSB formation and expand on the original concepts of gap repair during meiosis to include DNA gaps that are generated by Spo11 itself.

DOI: 10.1038/s41586-021-03389-3

Source: https://www.nature.com/articles/s41586-021-03389-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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

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