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二价离子在减数分裂重组过程中由DMC1介导的D环延伸调控中的作用。

The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination.

作者信息

Altmannova Veronika, Spirek Mario, Orlic Lucija, Jēkabsons Atis, Clarence Tereza, Henggeler Adrian, Mlcouskova Jarmila, Chaleil Raphaël A G, Matos Joao, Krejci Lumir

机构信息

Department of Biology, Masaryk University, Brno 62500, Czech Republic.

International Clinical Research Center, St. Anne's University Hospital, Brno 65691, Czech Republic.

出版信息

iScience. 2022 Oct 25;25(11):105439. doi: 10.1016/j.isci.2022.105439. eCollection 2022 Nov 18.

DOI:10.1016/j.isci.2022.105439
PMID:36388968
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9641244/
Abstract

During meiosis, programmed DNA double-strand breaks (DSBs) are repaired by homologous recombination. DMC1, a conserved recombinase, plays a central role in this process. DMC1 promotes DNA strand exchange between homologous chromosomes, thus creating the physical linkage between them. Its function is regulated not only by several accessory proteins but also by bivalent ions. Here, we show that whereas calcium ions in the presence of ATP cause a conformational change within DMC1, stimulating its DNA binding and D-loop formation, they inhibit the extension of the invading strand within the D-loop. Based on structural studies, we have generated mutants of two highly conserved amino acids - E162 and D317 - in human DMC1, which are deficient in calcium regulation. studies of their yeast homologues further showed that they exhibit severe defects in meiosis, thus emphasizing the importance of calcium ions in the regulation of DMC1 function and meiotic recombination.

摘要

在减数分裂过程中，程序性DNA双链断裂（DSB）通过同源重组进行修复。DMC1是一种保守的重组酶，在这一过程中起核心作用。DMC1促进同源染色体之间的DNA链交换，从而在它们之间形成物理连接。其功能不仅受几种辅助蛋白的调节，还受二价离子的调节。在这里，我们表明，在ATP存在的情况下，钙离子会导致DMC1内的构象变化，刺激其DNA结合和D环形成，但它们会抑制D环内侵入链的延伸。基于结构研究，我们在人DMC1中产生了两个高度保守氨基酸E162和D317的突变体，它们缺乏钙调节。对其酵母同源物的研究进一步表明，它们在减数分裂中表现出严重缺陷，从而强调了钙离子在调节DMC1功能和减数分裂重组中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/03803e9c049d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/80590a254127/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/8944ea32a113/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/5cdb68e656eb/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/62733f3f38bf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/f18d62c0cf60/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/0b0833d3d14a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/4043c13f84bc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/03803e9c049d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/80590a254127/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/8944ea32a113/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/5cdb68e656eb/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/62733f3f38bf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/f18d62c0cf60/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/0b0833d3d14a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/4043c13f84bc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dea/9641244/03803e9c049d/gr7.jpg

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Single-molecule visualization of human RECQ5 interactions with single-stranded DNA recombination intermediates.人类RECQ5与单链DNA重组中间体相互作用的单分子可视化
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Phosphorylation of the RecQ Helicase Sgs1/BLM Controls Its DNA Unwinding Activity during Meiosis and Mitosis.
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