The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.

IF 3.3 3区生物学

Genetics Pub Date : 2024-04-24 DOI:10.1093/genetics/iyae066

Gianno Pannafino, Jun Jie Chen, Viraj Mithani, Lisette Payero, Michael Gioia, J. B. Crickard, Eric Alani

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引用次数: 0

Abstract

The accurate segregation of homologous chromosomes during the Meiosis I reductional division in most sexually reproducing eukaryotes requires crossing over between homologs. In baker's yeast approximately 80 percent of meiotic crossovers result from Mlh1-Mlh3 and Exo1 acting to resolve double-Holliday junction (dHJ) intermediates in a biased manner. Little is known about how Mlh1-Mlh3 is recruited to recombination intermediates to perform its role in crossover resolution. We performed a gene dosage screen in baker's yeast to identify novel genetic interactors with Mlh1-Mlh3. Specifically, we looked for genes whose lowered dosage reduced meiotic crossing over using sensitized mlh3 alleles that disrupt the stability of the Mlh1-Mlh3 complex and confer defects in mismatch repair but do not disrupt meiotic crossing over. To our surprise we identified genetic interactions between MLH3 and DMC1, the recombinase responsible for recombination between homologous chromosomes during meiosis. We then showed that Mlh3 physically interacts with Dmc1 in vitro and in vivo. Partial complementation of Mlh3 crossover functions was observed when MLH3 was expressed under the control of the CLB1 promoter (NDT80 regulon), suggesting that Mlh3 function can be provided late in meiotic prophase at some functional cost. A model for how Dmc1 could facilitate Mlh1-Mlh3's role in crossover resolution is presented.

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Dmc1 重组酶与 Mlh1-Mlh3 内切酶发生物理作用，并促进减数分裂交叉功能。

在大多数有性生殖真核生物的减数第一次还原分裂过程中，同源染色体的准确分离需要同源染色体之间的交叉。在面包酵母中，大约 80% 的减数分裂交叉是由 Mlh1-Mlh3 和 Exo1 以偏向的方式作用于双霍利迪连接（dHJ）中间体而产生的。人们对 Mlh1-Mlh3 如何被招募到重组中间体以发挥其解决交叉的作用知之甚少。我们在面包酵母中进行了基因剂量筛选，以确定与 Mlh1-Mlh3 相互作用的新基因。具体来说，我们使用敏化的 mlh3 等位基因来寻找剂量降低会减少减数分裂交叉的基因，这些基因会破坏 Mlh1-Mlh3 复合物的稳定性，导致错配修复缺陷，但不会破坏减数分裂交叉。令我们惊讶的是，我们发现了 MLH3 和 DMC1 之间的遗传相互作用，DMC1 是减数分裂过程中负责同源染色体间重组的重组酶。我们随后发现，Mlh3 与 Dmc1 在体外和体内都有物理相互作用。当MLH3在CLB1启动子（NDT80调控子）的控制下表达时，可观察到Mlh3交叉功能的部分互补，这表明Mlh3的功能可在减数分裂前期的晚期以一定的功能代价提供。本文提出了一个模型，说明 Dmc1 如何促进 Mlh1-Mlh3 在交叉解析中发挥作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics 生物-遗传学

CiteScore

6.20

自引率

6.10%

发文量

177

期刊介绍： GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.