Sororin Mediates Sister Chromatid Cohesion by Antagonizing Wapl

Abstract

Sister chromatid cohesion is essential for chromosome segregation and is mediated by cohesin bound to DNA. Cohesin-DNA interactions can be reversed by the cohesion-associated protein Wapl, whereas a stably DNA-bound form of cohesin is thought to mediate cohesion. In vertebrates, Sororin is essential for cohesion and stable cohesin-DNA interactions, but how Sororin performs these functions is unknown. We show that DNA replication and cohesin acetylation promote binding of Sororin to cohesin, and that Sororin displaces Wapl from its binding partner Pds5. In the absence of Wapl, Sororin becomes dispensable for cohesion. We propose that Sororin maintains cohesion by inhibiting Wapl's ability to dissociate cohesin from DNA. Sororin has only been identified in vertebrates, but we show that many invertebrate species contain Sororin-related proteins, and that one of these, Dalmatian, is essential for cohesion in Drosophila. The mechanism we describe here may therefore be widely conserved among different species.

C-terminus of Sororin interacts with SA2 and regulates sister chromatid cohesion

“…3,7,22 However, it is unclear which cohesin subunit that Sororin binds to. We report herein that Sororin binds to cohesin-SA2 through its C-terminus and plays an important role in sister chromatid cohesion and separation.…”

“…4,5 Acetyltransferases, Eco1 vertebrate orthologs Esco1 and Esco2, are essential for acetylation of Smc3, a step required for the recruitment of Sororin and the generation of sister chromatid cohesion during DNA replication. [6][7][8][9] The cohesin-associated Sororin maintains the sister chromatid cohesion established at S phase until Sororin is phosphorylated and dissociated from chromatids, when Wapl forms a complex with Pds5 to remove cohesin in prophase/prometaphase. 7,[10][11][12][13][14][15] In addition, Sororin plays a regulatory role in the resolution of sister chromatid cohesion during M-phase.…”

“…[6][7][8][9] The cohesin-associated Sororin maintains the sister chromatid cohesion established at S phase until Sororin is phosphorylated and dissociated from chromatids, when Wapl forms a complex with Pds5 to remove cohesin in prophase/prometaphase. 7,[10][11][12][13][14][15] In addition, Sororin plays a regulatory role in the resolution of sister chromatid cohesion during M-phase. 3,15 Sororin can co-immunoprecipitate (co-IP) cohesin core subunits Rad21, Smc1, Smc3, and SA1/2, as well as cohesin-associated protein Pds5A/B and Wapl.…”

“…3,15 Sororin can co-immunoprecipitate (co-IP) cohesin core subunits Rad21, Smc1, Smc3, and SA1/2, as well as cohesin-associated protein Pds5A/B and Wapl. 7,16 The C-terminus of Sororin is known to be responsible for interaction with cohesin, 17 but which cohesin core subunit Sororin binds remains unknown. Here we report that the last 12 amino acid (aa) residues of Sororin are required to interact with cohesin core subunit SA2, and that deletion of these 12aa residues not only inhibits the interaction of Sororin and cohesin, but also fails to rescue the precocious chromosome separation (PCS) caused by the silencing of endogenous Sororin.…”

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

“…Establishment of stable cohesion further requires acetyl modifications on the DNA sensing lysines of the Smc3 head by the acetyltransferase Eco1 [61–64]. This acetylation counteracts Wapl-driven cohesin release, probably by direct inhibition and/or recruitment of antagonizing factors such as sororin [37,65]. As a result, cohesion is maintained until the onset of anaphase.…”