Wang Menglu, Robertson Daniel, Zou Juan, Spanos Christos, Rappsilber Juri, Marston Adele L
Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, United Kingdom.
Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355, Berlin, Germany.
EMBO J. 2025 Feb;44(3):705-735. doi: 10.1038/s44318-024-00336-6. Epub 2024 Dec 17.
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.
基因组由染色体结构维持(SMC)蛋白组织成DNA环。SMC为DNA修复、基因表达和染色体分离建立功能性染色体亚结构域,但SMC活性如何被特异性靶向尚不清楚。在这里,我们定义了在芽殖酵母中将凝聚素SMC复合物靶向特定染色体区域的分子机制。凝聚素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。在有丝分裂早期,受体Sgo1和Lrs4中的CR1基序分别将凝聚素招募到着丝粒周围区域和核糖体DNA(rDNA),以促进姐妹动粒双定向和rDNA凝聚。我们还发现,染色体臂凝聚在姐妹动粒受到张力时开始,其方式依赖于Ycg1口袋。我们提出,多种含CR1的蛋白将凝聚素招募到染色体上,并根据其序列鉴定出几个额外的候选蛋白。总体而言,我们揭示了将凝聚素靶向以使染色体结构域功能化从而在有丝分裂期间实现准确染色体分离的分子机制。