Establishment of Sister Chromatid Cohesion

The cohesin complex loads onto chromatin in telophase, but its association with chromatin remains transient, dynamic until the S-phase of the cell cycle, presumably because the cohesin-bound NIPBL:MAU2 (SCC2:SCC4) complex promotes chromatin loading, while cohesin-bound WAPAL promotes dissociation from chromatin. Stable binding of cohesin complexes to chromatin, measured by a mean residence time on chromatin, is triggered by DNA replication in S-phase (Gerlich et al. 2006), consistent with establishment of sister chromatid cohesion. <br><br> In S-phase, acetyltransferases ESCO1 and ESCO2 acetylate the SMC3 cohesin subunit (Hou and Zou 2005, Zhang et al. 2008, Nishiyama et al. 2010, Whelan et al. 2012). The acetylation of SMC3, in addition to DNA replication and the presence of PDS5 on cohesin, facilitates the recruitment of CDCA5 (Sororin) to cohesin complexes, an essential step in the establishment of sister chromatid cohesion in mammalian cells (Rankin et al. 2005, Nishiyama et al. 2010). CDCA5 (Sororin) displaces WAPAL from PDS5, thus preventing WAPAL to interfere with the establishment of sister chromatid cohesion (Nishiyama et al. 2010). The establishment and temporal regulation of sister chromatid cohesion is necessary for equal segregation of replicated chromosomes to daughter cells.

凝聚复合体在细胞周期的终末期加载至染色质上，但其与染色质的结合呈现为短暂且动态的状态，直至细胞周期的S期。这一现象推测与凝聚蛋白结合的NIPBL:MAU2（即SCC2:SCC4）复合体促进染色质加载，以及凝聚蛋白结合的WAPAL促进从染色质解离有关。通过衡量凝聚复合体在染色质上的平均停留时间来测定的稳定结合，由S期的DNA复制触发（Gerlich等，2006年），这与姐妹染色单体凝聚的建立一致。在S期，乙酰转移酶ESCO1和ESCO2乙酰化SMC3凝聚子单元（Hou和Zou，2005年，Zhang等，2008年，Nishiyama等，2010年，Whelan等，2012年）。SMC3的乙酰化，除了DNA复制和凝聚蛋白上的PDS5的存在外，还促进了CDCA5（Sororin）向凝聚复合体的募集，这是哺乳动物细胞中建立姐妹染色单体凝聚的必要步骤（Rankin等，2005年，Nishiyama等，2010年）。CDCA5（Sororin）从PDS5中取代WAPAL，从而防止WAPAL干扰姐妹染色单体凝聚的建立（Nishiyama等，2010年）。姐妹染色单体凝聚的建立及其时间调控对于复制染色体的均等分离至子细胞是必要的。