Chromosome cohesion – rings, knots, orcs and fellowship

Abstract

Sister-chromatid cohesion is essential for accurate chromosome segregation. A key discovery towards our understanding of sister-chromatid cohesion was made 10 years ago with the identification of cohesins. Since then, cohesins have been shown to be involved in cohesion in numerous organisms, from yeast to mammals. Studies of the composition, regulation and structure of the cohesin complex led to a model in which cohesin loading during S-phase establishes cohesion, and cohesin cleavage at the onset of anaphase allows sister-chromatid separation. However, recent studies have revealed activities that provide cohesion in the absence of cohesin. Here we review these advances and propose an integrative model in which chromatid cohesion is a result of the combined activities of multiple cohesion mechanisms.

The Precarious Prokaryotic Chromosome

“…SCC guards the critical period of maturation of nascent DNA, during which at least four important tasks must be accomplished: (i) introduction of the regular coiling into the newly synthesized duplexes that emerge from the replisomes essentially paranemic, without coils; (ii) linking of Okazaki fragments together (86); (iii) repairing of persistent single-strand gaps and double-strand breaks (87); and (iv) removing the precatenanes that always accumulate behind replication forks (88,89). In eukaryotic chromosomes, sister-chromatid cohesion is protein-(cohesin)-mediated and lasts several hours, encompassing the whole S, the whole G 2 , and part of the M phase until chromatid separation occurs (90). Completely replicated chromosomes do retain a low level of catenation, but it is not responsible for holding sister chromatids together (91).…”

Cohesin codes – interpreting chromatin architecture and the many facets of cohesin function

“…The highly conserved nature of SMC complexes provides crucial insight into the structure of cohesion but, thus far, remain largely underutilized. For instance, analyses of interactions of cohesin subunits and their release upon linearization of circular DNA Gruber et al, 2003;Ivanov and Nasmyth, 2005;Haering et al, 2008;Farcas et al, 2011) led to a model in which huge cohesin rings encircle DNA (for alternative models, see McNairn and Gerton, 2008;Skibbens, 2008;Onn et al, 2008;Díaz-Martínez et al, 2008;Nasmyth and Haering, 2009). The presumption that DNA is embraced by SMC arms, however, is speculative, lacks support from DNA-protein mapping studies and is confounded by findings that Smc1 and Smc3 heads remain closely apposed during anaphase (Mc Intyre et al, 2007).…”

Sororin is tethered to Cohesin SA2

“…There are 2 overarching mechanisms that account for the cohesion that is maintained between the sisters. 1 Firstly, the nascent DNA molecules emerge from the replicative machinery as physically entwined, or catenated, entities. These cannot be resolved from each other without coupled DNA breakage and re-ligation, known as strand passage reactions, that are completed by Type II topoisomerases in preparation for chromatid segregation.…”