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Molecular mechanism targeting condensin for chromosome condensation.
The EMBO Journal ( IF 9.4 ) Pub Date : 2024-12-17 , DOI: 10.1038/s44318-024-00336-6 Menglu Wang,Daniel Robertson,Juan Zou,Christos Spanos,Juri Rappsilber,Adele L Marston
The EMBO Journal ( IF 9.4 ) Pub Date : 2024-12-17 , DOI: 10.1038/s44318-024-00336-6 Menglu Wang,Daniel Robertson,Juan Zou,Christos Spanos,Juri Rappsilber,Adele L Marston
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.
中文翻译:
靶向凝聚素进行染色体浓缩的分子机制。
基因组通过染色体结构维护 (SMC) 蛋白组织成 DNA 环。SMC 建立功能性染色体亚结构域用于 DNA 修复、基因表达和染色体分离,但 SMC 活性如何特异性靶向尚不清楚。在这里,我们定义了将凝聚素 SMC 复合物靶向出芽酵母中特定染色体区域的分子机制。缩归素 HAWK 亚基 Ycg1 上的保守口袋与携带相关基序 CR1 的染色体受体结合。在有丝分裂早期,受体 Sgo1 和 Lrs4 中的 CR1 基序将凝聚素募集到着丝粒周围和 rDNA,以分别促进姐妹着丝粒双向和 rDNA 凝聚。我们还发现,染色体臂浓缩始于姐妹着丝粒受到张力,其方式取决于 Ycg1 口袋。我们提出多个含有 CR1 的蛋白质将凝聚素募集到染色体上,并根据它们的序列鉴定几个额外的候选者。总体而言,我们揭示了靶向凝聚素使染色体结构域功能化以在有丝分裂过程中实现准确染色体分离的分子机制。
更新日期:2024-12-17
中文翻译:
靶向凝聚素进行染色体浓缩的分子机制。
基因组通过染色体结构维护 (SMC) 蛋白组织成 DNA 环。SMC 建立功能性染色体亚结构域用于 DNA 修复、基因表达和染色体分离,但 SMC 活性如何特异性靶向尚不清楚。在这里,我们定义了将凝聚素 SMC 复合物靶向出芽酵母中特定染色体区域的分子机制。缩归素 HAWK 亚基 Ycg1 上的保守口袋与携带相关基序 CR1 的染色体受体结合。在有丝分裂早期,受体 Sgo1 和 Lrs4 中的 CR1 基序将凝聚素募集到着丝粒周围和 rDNA,以分别促进姐妹着丝粒双向和 rDNA 凝聚。我们还发现,染色体臂浓缩始于姐妹着丝粒受到张力,其方式取决于 Ycg1 口袋。我们提出多个含有 CR1 的蛋白质将凝聚素募集到染色体上,并根据它们的序列鉴定几个额外的候选者。总体而言,我们揭示了靶向凝聚素使染色体结构域功能化以在有丝分裂过程中实现准确染色体分离的分子机制。