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黏合蛋白 SOLO 与 SMC1 结合,对于果蝇减数分裂中的联会、重组、同源偏爱以及着丝粒的黏合和配对是必需的。

The cohesion protein SOLO associates with SMC1 and is required for synapsis, recombination, homolog bias and cohesion and pairing of centromeres in Drosophila Meiosis.

机构信息

Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, USA.

出版信息

PLoS Genet. 2013;9(7):e1003637. doi: 10.1371/journal.pgen.1003637. Epub 2013 Jul 18.

Abstract

Cohesion between sister chromatids is mediated by cohesin and is essential for proper meiotic segregation of both sister chromatids and homologs. solo encodes a Drosophila meiosis-specific cohesion protein with no apparent sequence homology to cohesins that is required in male meiosis for centromere cohesion, proper orientation of sister centromeres and centromere enrichment of the cohesin subunit SMC1. In this study, we show that solo is involved in multiple aspects of meiosis in female Drosophila. Null mutations in solo caused the following phenotypes: 1) high frequencies of homolog and sister chromatid nondisjunction (NDJ) and sharply reduced frequencies of homolog exchange; 2) reduced transmission of a ring-X chromosome, an indicator of elevated frequencies of sister chromatid exchange (SCE); 3) premature loss of centromere pairing and cohesion during prophase I, as indicated by elevated foci counts of the centromere protein CID; 4) instability of the lateral elements (LE)s and central regions of synaptonemal complexes (SCs), as indicated by fragmented and spotty staining of the chromosome core/LE component SMC1 and the transverse filament protein C(3)G, respectively, at all stages of pachytene. SOLO and SMC1 are both enriched on centromeres throughout prophase I, co-align along the lateral elements of SCs and reciprocally co-immunoprecipitate from ovarian protein extracts. Our studies demonstrate that SOLO is closely associated with meiotic cohesin and required both for enrichment of cohesin on centromeres and stable assembly of cohesin into chromosome cores. These events underlie and are required for stable cohesion of centromeres, synapsis of homologous chromosomes, and a recombination mechanism that suppresses SCE to preferentially generate homolog crossovers (homolog bias). We propose that SOLO is a subunit of a specialized meiotic cohesin complex that mediates both centromeric and axial arm cohesion and promotes homolog bias as a component of chromosome cores.

摘要

姐妹染色单体之间的黏合由黏合蛋白介导,对于姐妹染色单体和同源染色体的正确减数分裂分离至关重要。solo 编码一种果蝇减数分裂特异性黏合蛋白,与黏合蛋白没有明显的序列同源性,在雄性减数分裂中需要它来维持着丝粒黏合、姐妹着丝粒的正确定向以及黏合蛋白亚基 SMC1 向着丝粒的富集。在这项研究中,我们表明 solo 参与了雌性果蝇减数分裂的多个方面。solo 缺失突变导致以下表型:1)同源染色体和姐妹染色单体非分离(NDJ)的频率很高,同源染色体交换的频率明显降低;2)环 X 染色体的传递减少,这是姐妹染色单体交换(SCE)频率升高的一个指标;3)前期 I 时着丝粒配对和黏合过早丢失,这表现为着丝粒蛋白 CID 的焦点计数升高;4)联会复合体(SCs)的侧体(LE)和中央区不稳定,这表现为染色体核心/LE 成分 SMC1 和横向细丝蛋白 C(3)G 的染色分别呈片段化和点状,在整个粗线期的各个阶段都是如此。SOLO 和 SMC1 在整个前期 I 都富集在着丝粒上,沿着 SC 的 LE 共排列,并从卵巢蛋白提取物中相互共免疫沉淀。我们的研究表明,SOLO 与减数分裂黏合蛋白密切相关,不仅需要将黏合蛋白富集在着丝粒上,还需要将黏合蛋白稳定地组装到染色体核心中。这些事件是稳定着丝粒黏合、同源染色体联会以及优先产生同源交叉(同源偏好)的重组机制所必需的。我们提出,SOLO 是一种特殊的减数分裂黏合蛋白复合物的亚基,该复合物介导着丝粒和轴臂的黏合,并作为染色体核心的一部分促进同源偏好。

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