Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London WC2A 3LY, UK.
Nucleic Acids Res. 2014 Jan;42(1):340-8. doi: 10.1093/nar/gkt882. Epub 2013 Sep 22.
The condensin complex is a key determinant of mitotic chromosome architecture. In addition, condensin promotes resolution of sister chromatids during anaphase, a function that is conserved from prokaryotes to human. Anaphase bridges observed in cells lacking condensin are reminiscent of chromosome segregation failure after inactivation of topoisomerase II (topo II), the enzyme that removes catenanes persisting between sister chromatids following DNA replication. Circumstantial evidence has linked condensin to sister chromatid decatenation but, because of the difficulty of observing chromosome catenation, this link has remained indirect. Alternative models for how condensin facilitates chromosome resolution have been put forward. Here, we follow the catenation status of circular minichromosomes of three sizes during the Saccharomyeces cerevisiae cell cycle. Catenanes are produced during DNA replication and are for the most part swiftly resolved during and following S-phase, aided by sister chromatid separation. Complete resolution, however, requires the condensin complex, a dependency that becomes more pronounced with increasing chromosome size. Our results provide evidence that condensin prevents deleterious anaphase bridges during chromosome segregation by promoting sister chromatid decatenation.
凝聚复合物是有丝分裂染色体结构的关键决定因素。此外,凝聚物促进后期姐妹染色单体的分辨率,这一功能从原核生物到人类都是保守的。在缺乏凝聚物的细胞中观察到的后期桥类似于拓扑异构酶 II(topo II)失活后染色体分离失败,topo II 是一种在 DNA 复制后去除姐妹染色单体之间持续存在的连环的酶。凝聚物与姐妹染色单体解连环之间的联系已有间接证据,但由于观察染色体连环的难度,这种联系仍然是间接的。提出了替代模型来解释凝聚物如何促进染色体分辨率。在这里,我们在酿酒酵母细胞周期中跟踪三种大小的圆形微染色体的连环状态。在 DNA 复制过程中产生连环,并且在 S 期期间和之后大部分迅速得到解决,这得益于姐妹染色单体的分离。然而,完全解决需要凝聚复合物,随着染色体大小的增加,这种依赖性变得更加明显。我们的结果提供了证据,证明凝聚物通过促进姐妹染色单体解连环来防止有丝分裂过程中有害的后期桥。