Crossovers are regulated by a conserved and disordered synaptonemal complex domain.

IF 13.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nucleic Acids Research Pub Date : 2025-02-08 DOI:10.1093/nar/gkaf095
Ana Rita Rodrigues Neves, Ivana Čavka, Tobias Rausch, Simone Köhler
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Abstract

During meiosis, the number and distribution of crossovers (COs) must be precisely regulated through CO assurance and interference to prevent chromosome missegregation and genomic instability in the progeny. Here we show that this regulation of COs depends on a disordered and conserved domain within the synaptonemal complex (SC). This domain is located at the C-terminus of the central element protein SYP-4 in Caenorhabditis elegans. While not necessary for synapsis, the C-terminus of SYP-4 is crucial for both CO assurance and interference. Although the SYP-4 C-terminus contains many potential phosphorylation sites, we found that phosphorylation is not the primary regulator of CO events. Instead, we discovered that nine conserved phenylalanines are required to recruit a pro-CO factor predicted to be an E3 ligase and regulate the physical properties of the SC. We propose that this conserved and disordered domain plays a crucial role in maintaining the SC in a state that allows transmitting signals to regulate CO formation. While the underlying mechanisms remain to be fully understood, our findings align with existing models suggesting that the SC plays a critical role in determining the number and distribution of COs along chromosomes, thereby safeguarding the genome for future generations.

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交叉是由一个保守的和无序的突触复合体域调节的。
在减数分裂过程中,必须通过CO保证和干扰来精确调控杂交的数量和分布,以防止后代染色体错分离和基因组不稳定。在这里,我们表明这种COs的调节依赖于突触复合体(SC)内的无序和保守结构域。该结构域位于秀丽隐杆线虫中心元件蛋白SYP-4的c端。SYP-4的c端虽然不是突触所必需的,但对CO的保证和干扰都至关重要。尽管SYP-4 c端含有许多潜在的磷酸化位点,但我们发现磷酸化并不是CO事件的主要调节因子。相反,我们发现需要9个保守的苯丙氨酸来招募一个被预测为E3连接酶的前CO因子并调节SC的物理性质。我们提出,这个保守的和无序的结构域在维持SC处于允许传递信号调节CO形成的状态中起着至关重要的作用。虽然潜在的机制仍有待充分了解,但我们的发现与现有的模型一致,表明SC在决定COs沿染色体的数量和分布方面起着关键作用,从而为后代保护基因组。
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来源期刊
Nucleic Acids Research
Nucleic Acids Research 生物-生化与分子生物学
CiteScore
27.10
自引率
4.70%
发文量
1057
审稿时长
2 months
期刊介绍: Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.
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