Molecular mechanism targeting condensin for chromosome condensation.

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2025-02-01 Epub Date: 2024-12-17 DOI:10.1038/s44318-024-00336-6
Menglu Wang, Daniel Robertson, Juan Zou, Christos Spanos, Juri Rappsilber, Adele L Marston
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Abstract

Genomes are organised into DNA loops by the Structural Maintenance of Chromosomes (SMC) proteins. SMCs establish functional chromosomal sub-domains for DNA repair, gene expression and chromosome segregation, but how SMC activity is specifically targeted is unclear. Here, we define the molecular mechanism targeting the condensin SMC complex to specific chromosomal regions in budding yeast. A conserved pocket on the condensin HAWK subunit Ycg1 binds to chromosomal receptors carrying a related motif, CR1. In early mitosis, CR1 motifs in receptors Sgo1 and Lrs4 recruit condensin to pericentromeres and rDNA, to facilitate sister kinetochore biorientation and rDNA condensation, respectively. We additionally find that chromosome arm condensation begins as sister kinetochores come under tension, in a manner dependent on the Ycg1 pocket. We propose that multiple CR1-containing proteins recruit condensin to chromosomes and identify several additional candidates based on their sequence. Overall, we uncover the molecular mechanism that targets condensin to functionalise chromosomal domains to achieve accurate chromosome segregation during mitosis.

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以凝集素为染色体凝聚靶标的分子机制
基因组由染色体结构维护(SMC)蛋白组织成DNA环。SMCs建立了DNA修复、基因表达和染色体分离的功能染色体亚域,但SMC活性如何特异性靶向尚不清楚。在这里,我们定义了在出芽酵母中针对凝缩蛋白SMC复合体特定染色体区域的分子机制。凝缩蛋白HAWK亚基Ycg1上的一个保守口袋与携带相关基序CR1的染色体受体结合。在早期有丝分裂中,受体Sgo1和Lrs4中的CR1基序将凝缩蛋白分别招募到中心粒和rDNA中,以促进姐妹着丝点的双向定向和rDNA的凝聚。我们还发现,当姐妹着丝点受到压力时,染色体臂凝结就开始了,其方式取决于Ycg1口袋。我们提出多种含cr1的蛋白将凝聚蛋白招募到染色体上,并根据它们的序列确定了几个额外的候选蛋白。总的来说,我们揭示了靶向凝缩蛋白功能化染色体结构域的分子机制,以在有丝分裂期间实现准确的染色体分离。
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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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