Drosophila Dalmatian combines sororin and shugoshin roles in establishment and protection of cohesion

Abstract

Sister chromatid cohesion is crucial to ensure chromosome bi-orientation and equal chromosome segregation. Cohesin removal via mitotic kinases and Wapl has to be prevented in pericentromeric regions in order to protect cohesion until metaphase, but the mechanisms of mitotic cohesion protection remain elusive in Here, we show that dalmatian (Dmt), an ortholog of the vertebrate cohesin-associated protein sororin, is required for protection of mitotic cohesion in flies. Dmt is essential for cohesion establishment during interphase and is enriched on pericentromeric heterochromatin. Dmt is recruited through direct association with heterochromatin protein-1 (HP1), and this interaction is required for cohesion. During mitosis, Dmt interdependently recruits protein phosphatase 2A (PP2A) to pericentromeric regions, and PP2A binding is required for Dmt to protect cohesion. Intriguingly, Dmt is sufficient to protect cohesion upon heterologous expression in human cells. Our findings of a hybrid system, in which Dmt exerts both sororin-like establishment functions and shugoshin-like heterochromatin-based protection roles, provide clues to the evolutionary modulation of eukaryotic cohesion regulation systems.

Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function

“…As shown in S1I Figure the effects on cohesion factor transcript levels are all less than 2-fold, making it unlikely that they are involved in the substantial changes in sister chromatid cohesion observed in the Pds5 depletion and their suppression in the Pds5-Brca2 codepletion. Pds5 and Brca2 depletion both modestly reduce Nipped-B RNA levels by 30 to 40%, and increase transcripts of the Smc1, Smc3, wapl, eco, and dmt (dalmatian, encoding a sororinshugoshin fusion protein [15,16]) gene up to 1.5-fold, none of which explains the opposing effects of Pds5 and Brca2 on sister cohesion. The only significant effect of the double Pds5-Brca2 depletion that is not observed in the single depletions is a 40% reduction in SA transcripts, which should reduce, not rescue cohesion if it were of sufficient magnitude to actually have an effect (S1I Fig).…”

Dalmatian: spotting the difference in cohesin protectors

“…Until now, it was unclear whether cohesin maintenance factors are similarly required in organisms other than vertebrates, as no protective function had been observed for shugoshins, and sororin does not appear to be universally present in eukaryotes. The new findings from Nishiyama and colleagues (Yamada et al , ) demonstrate that, remarkably, the functions of sororin and shugoshin are conferred by a single hybrid protein, Dalmatian ( Dmt ), in Drosophila mitosis (Fig ). The new study demonstrates the evolutionary importance of cohesin maintenance pathways and raises the intriguing possibility that variations on this theme will be identified in other organisms in the future.…”

“…(A) The tripartite cohesin ring and its accessory proteins are conserved between vertebrates and Drosophila , but the sororin and shugoshin regulators are combined in a single protein called Dalmatian (Dmt) in flies. (B) Domain structure of Dalmatian indicating the binding domains mapped by Yamada et al ().…”

SWITCH 1/DYAD is a novel WINGS APART-LIKE antagonist that maintains sister chromatid cohesion in meiosis

“…The precise establishment, maintenance, and removal of sister chromatid cohesion is essential for faithful chromosome segregation in both mitosis and meiosis. In contrast to the well-described mechanisms of cohesion regulation in mitosis 17,18,20 , much less is known about the control of cohesion in meiosis. Our study in Arabidopsis provides evidence that the prophase pathway of cohesion regulation exists in meiosis including the inhibition of the cohesin remodeler WAPL by a new type of inhibitor represented by the previously identified protein SWI1 that functions and is regulated in a amazingly similar fashion as Sororin in animals.…”