Sister Chromatid Cohesion: A Simple Concept with a Complex Reality

Abstract

In eukaryotes, the process of sister chromatid cohesion holds the two sister chromatids (the replicated chromosomes) together from DNA replication to the onset of chromosome segregation. Cohesion is mediated by cohesin, a four-subunit SMC (structural maintenance of chromosome) complex. Cohesin and cohesion are required for proper chromosome segregation, DNA repair, and gene expression. To carry out these functions, cohesion is regulated by elaborate mechanisms involving a growing list of cohesin auxiliary factors. These factors control the timing and position of cohesin binding to chromatin, activate chromatin-bound cohesin to become cohesive, and orchestrate the orderly dissolution of cohesion. The 45-nm ringlike architecture of soluble cohesin is compatible with dramatically different mechanisms for both chromatin binding and cohesion generation. Solving the mechanism of cohesion and its complex regulation presents significant challenges but offers the potential to provide important insights into higher-order chromosome organization and chromosome biology.

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

“…148 Cohesin rings encircle two replicated daughter chromatids and thereby maintain, through a topological confinement, the cohesion of chromatids until mitosis. [231][232][233] An endoprotease called separase is activated during mitosis and cleaves the Scc1/Rad21 (kleisin) subunit, thereby opening the ring of cohesin and making chromatid separation possible. In the yeast Saccharomyces cerevisiae, the C-terminal fragment of separase-cleaved Scc1/Rad21 bears N-terminal Arg, a destabilizing residue [ Fig.…”

Timeless functions independently of the Tim-Tipin complex to promote sister chromatid cohesion in normal human fibroblasts

“…The loading of cohesin onto chromatin, the establishment of SCC and the maintenance and dissolution of cohesion are cell cycle-regulated processes. 23 Defective SCC is associated with developmental genetic disorders, including Roberts syndrome, Cordelia de Lange syndrome and Warsaw breakage syndrome, 24,25 and mutations in SCC genes have been detected in cancers. 26 Large-scale genetic screens in yeast have revealed an intricate network of interactions among DNA replication, checkpoint activation and SCC.…”

“…30 Some models posit that the association of cohesin rings with replisomes may require pausing of replication forks 23,30 an event that would require replisome stabilization through Tim-Tipin and Claspin. 19,20,31 The studies described here examined whether Timeless, Tipin and Claspin contribute to SCC in genetically stable, diploid human fibroblasts as part of, or independently of, their interactions with the checkpoint kinases ATR and Chk1.…”

Untimely expression of gametogenic genes in vegetative cells causes uniparental disomy

“…Since RNAi is required for centromeric heterochromatin assembly, we wondered whether UPD is caused by defects in heterochromatin-dependent loading of cohesin at pericentromeric regions 5,6,8 . The loss of heterochromatin assembly factor Clr4 abolishes cohesin localization at centromeres (Extended Data Fig.…”