The conserved AAA ATPase PCH-2 distributes its regulation of meiotic prophase events through multiple meiotic HORMADs in C. elegans.
The conserved AAA ATPase PCH-2 distributes its regulation of meiotic prophase events through multiple meiotic HORMADs in C. elegans.
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DOI：
10.1371/journal.pgen.1010708
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发表时间：
2023-04
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
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During meiotic prophase, the essential events of homolog pairing, synapsis, and recombination are coordinated with meiotic progression to promote fidelity and prevent aneuploidy. The conserved AAA+ ATPase PCH-2 coordinates these events to guarantee crossover assurance and accurate chromosome segregation. How PCH-2 accomplishes this coordination is poorly understood. Here, we provide evidence that PCH-2 decelerates pairing, synapsis and recombination in C. elegans by remodeling meiotic HORMADs. We propose that PCH-2 converts the closed versions of these proteins, which drive these meiotic prophase events, to unbuckled conformations, destabilizing interhomolog interactions and delaying meiotic progression. Further, we find that PCH-2 distributes this regulation among three essential meiotic HORMADs in C. elegans: PCH-2 acts through HTP-3 to regulate pairing and synapsis, HIM-3 to promote crossover assurance, and HTP-1 to control meiotic progression. In addition to identifying a molecular mechanism for how PCH-2 regulates interhomolog interactions, our results provide a possible explanation for the expansion of the meiotic HORMAD family as a conserved evolutionary feature of meiosis. Taken together, our work demonstrates that PCH-2’s remodeling of meiotic HORMADs has functional consequences for the rate and fidelity of homolog pairing, synapsis, recombination and meiotic progression, ensuring accurate meiotic chromosome segregation. Sexual reproduction relies on production of gametes, such as eggs and sperm, which are produced during meiosis. During this specialized cell division, chromosomes replicate, pair with their homologs, undergo synapsis and finally undergo recombination, all of which are required for correct meiotic chromosome segregation. How these events are coordinated with each other, and the cell cycle, to ensure that they occur with fidelity is not well understood. In previous work, we showed that the conserved enzyme PCH-2 coordinates homolog pairing, synapsis and recombination in the nematode C. elegans. Here, we show that PCH-2 accomplishes this coordination by distributing its regulation of these events through different members of the meiotic HORMAD protein family: PCH-2 controls pairing and synapsis through HTP-3, recombination through HIM-3 and meiotic progression through HTP-1. Moreover, this distribution may explain why there are so many meiotic HORMADs in C. elegans. Finally, we provide a model for how PCH-2 may be modifying meiotic HORMADs through its enzymatic function, molecularly explaining its role in pairing, synapsis, recombination and meiotic progression.
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影响因子：
6.9
作者：
Cuacos M;Lambing C;Pachon-Penalba M;Osman K;Armstrong SJ;Henderson IR;Sanchez-Moran E;Franklin FCH;Heckmann S
通讯作者：
Heckmann S
影响因子：
11.8
作者：
Colaiácovo, MP;MacQueen, AJ;Villeneuve, AM
通讯作者：
Villeneuve, AM
影响因子：
11.8
作者：
Couteau, Florence;Zetka, Monique
通讯作者：
Zetka, Monique
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
3.3
作者：
Bohr, Tisha;Ashley, Guinevere;Bhalla, Needhi
通讯作者：
Bhalla, Needhi