Molecular basis for condensin enrichment at pericentromeres [Brn1_ChIP-seq]

Faithful chromosome segregation requires packaging of the genome on both global and local scales. Condensin plays a crucial role at pericentromeres to resist spindle forces and ensure the oriented attachment of kinetochores to microtubules at mitosis. Here we demonstrate that budding yeast condensin is recruited to pericentromeres through a direct interaction between its Ycg1 subunit and the pericentromeric adaptor protein, shugoshin (Sgo1). We identify a Short Linear Motif (SLiM), termed CR1, within the C-terminal region of Sgo1 which inserts into a conserved pocket on Ycg1. Disruption of this interface abolishes the Sgo1-condensin interaction, prevents condensin recruitment to pericentromeres and results in defective sister kinetochore biorientation in mitosis. Similar motifs to CR1 are found in known and potential condensin binding partners and the Ycg1 binding pocket is broadly conserved, including in mammalian CAP-G proteins. Overall, we uncover the molecular mechanism that targets condensin to define a specialized chromosomal domain.精准的染色体分离需要在全局与局部尺度下完成基因组的折叠组装。凝缩蛋白（condensin）在着丝粒旁区发挥关键作用，以抵御纺锤体拉力，并确保有丝分裂过程中动粒与微管的定向附着。本研究证实，酿酒酵母中的凝缩蛋白可通过其Ycg1亚基与着丝粒旁区衔接蛋白保护蛋白（shugoshin, Sgo1）的直接相互作用，被招募至着丝粒旁区。我们在Sgo1的C端区域鉴定出一段名为CR1的短线性基序（SLiM），该基序可嵌入Ycg1上的保守口袋中。破坏这一相互作用界面会阻断Sgo1与凝缩蛋白的结合，阻止凝缩蛋白向着丝粒旁区的招募，并导致有丝分裂中姐妹动粒双向定向出现缺陷。在已知及潜在的凝缩蛋白结合伴侣中，均发现了与CR1相似的基序；且Ycg1的结合口袋在进化上高度保守，包括哺乳动物的CAP-G蛋白在内。综上，本研究揭示了将凝缩蛋白靶向定位至特化染色体结构域的分子机制。