Roles of condensin complexes in the maintenance and functional expression of genome

在高等真核细胞中，存在两种凝缩蛋白复合物，称为凝缩蛋白I和凝缩蛋白II。两者在有丝分裂染色体的组装和分离过程中都起着重要而不同的作用。在本研究中，我们研究了由染色体组装和分离缺陷引起的染色体畸变。此外，可能导致凝缩蛋白I和凝缩蛋白II的不同动力学的潜在因素已经被寻找。(1)我们发现，临床细胞遗传学染色体制剂对染色体组装和分离相关的染色体缺陷的缺陷是无用的。另一方面，凝缩蛋白耗竭和复制胁迫共同作用导致Hela细胞有丝分裂染色体出现严重的形态缺陷。这些结果表明，除了染色质组装外，凝缩蛋白还可能在保护或维持染色体结构方面发挥作用。此外，未知的因素可能有助于染色体形态的形成。(2)我们建立了一种新的细胞学方法——单极制备，用于临床分析与染色体组装和分离缺陷相关的人类疾病。(3)我们发现浓缩蛋白I和浓缩蛋白II分别富集于中期染色体的r带和g带区域。此外，凝缩蛋白的分布模式似乎也与组蛋白修饰有关。(4)我们证明了凝缩蛋白II可能在HeLa细胞的s期与染色质结合。这一观察结果使我们能够提出一个工作假设，即凝聚蛋白II可能在协调两个不同的染色体事件中发挥作用，即S期的DNA复制和M期的染色体组装。

In higher eukaryotic cells, there exist two condensin complexes, known as condensin I and II. Both play essential yet distinct functions in the processes of mitotic chromosome assembly and segregation. In this study, we have investigated chromosomal aberrations caused by the defect of chromosome assembly and segregation. Further, potential factors that might contribute to the distinct dynamics of condensin I and II have been searched.(1) We found that clinical cytogenetic chromosome preparations is not useful for defection of chromosomal defects associated with chromosome assembly and segregation. On the other hand, combination of condensin-depletion and replicative stress caused severe morphological defects in mitotic chromosomes of Hela cells. These results suggest that condensin may play a role in protection or maintenance of chromosomal structure in addition to chromatin assembly. Moreover, unknown factor (s) might contribute to the formation of chromosome morphology.(2) We have established a new a cytological method, terms monopolar preparation, for clinical analysis of human diseases associated with defects of chromosome assembly and segregation.(3) We have found that condensins I and II tend to be enriched in R-band and G-band regions, respectively, on metaphase chromosomes. Further, condensin distribution pattern also seems to be related with histone modifications.(4) We demonstrated that condensin II may bind to chromatin during S-phase in HeLa cells. This obsevation allows us to propose the working hypothesis that condensin II may play a role in coordinating two distinct chromosome events, i., e., DNA replication in S phase and chromosome assembly in M phase.