Cohesin's Concatenation of Sister DNAs Maintains Their Intertwining

Abstract

SummaryThe contribution of DNA catenation to sister chromatid cohesion is unclear partly because it has never been observed directly within mitotic chromosomes. Differential sedimentation-velocity and gel electrophoresis reveal that sisters of 26 kb circular minichromosomes are held together by catenation as well as by cohesin. The finding that chemical crosslinking of cohesin's three subunit interfaces entraps sister DNAs of circular but not linear minichromosomes implies that cohesin functions using a topological principle. Importantly, cohesin holds both catenated and uncatenated DNAs together in this manner. In the vicinity of centromeres, catenanes are resolved by spindle forces, but linkages mediated directly by cohesin resist these forces even after complete decatenation. Crucially, persistence of catenation after S phase depends on cohesin. We conclude that by retarding Topo II-driven decatenation, cohesin mediates sister chromatid cohesion by an indirect mechanism as well as one involving entrapment of sister DNAs inside its tripartite ring.

“Breaking Up Is Hard to Do”: The Formation and Resolution of Sister Chromatid Intertwines

“…In the crowded post-replicative DNA environment of a cell, where the replicated chromosomes are intermingled and the two sister chromatids are closely juxtaposed by proteinaceous cohesin complexes, this is a potentially serious problem. Indeed, full cohesion of DNA plasmids by cohesin ensures maintenance of higher level of DNA catenation between them than is observed following cohesin removal [50]. Therefore, there are several overlapping mechanisms that ensure the full decatenation of sister chromatids in vivo by type II topoisomerases.…”

The Precarious Prokaryotic Chromosome

“…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). In contrast, in the prokaryotic chromosomes, the duration of sister-chromatid cohesion is short (only 6 min in the rapidly growing E. coli bacterium [92]) and the process is mostly mediated by precatenanes (93,94) (even though sister chromatids may be held together at late-segregating loci by a special protein [95]).…”

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).…”

“…First, yeast eco1 mutant cells contain sister chromatids that are fully decorated with cohesins and subsequently undergo DNA replication, yet sister chromatids remain untethered (Lengronne et al, 2006;Milutinovich et al, 2007;Skibbens et al, 1999;Tóth et al, 1999). In fact, less than 50% of chromatid-bound cohesins participate in cohesion (Farcas et al, 2011;Haering et al, 2008). The simplest interpretation for such a 'cohesin without cohesion' phenotype is that each sister is bound by individual cohesins that subsequently become tethered together (Fig.…”