PT  - JOURNAL ARTICLE
AU  - Hayley Porter
AU  - Yang Li
AU  - Wazeer Varsally
AU  - Maria Victoria Neguembor
AU  - Manuel Beltran
AU  - Dubravka Pezic
AU  - Laura Martin
AU  - Manuel Tavares Cornejo
AU  - Amandeep Bhamra
AU  - Silvia Surinova
AU  - Richard G. Jenner
AU  - Maria Pia Cosma
AU  - Suzana Hadjur
TI  - STAG proteins promote cohesin ring loading at R-loops
AID  - 10.1101/2021.02.20.432055
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.20.432055
4099  - http://biorxiv.org/content/early/2021/02/20/2021.02.20.432055.short
4100  - http://biorxiv.org/content/early/2021/02/20/2021.02.20.432055.full
AB  - Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in cohesins localization to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin and interact with CTCF, as well as a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA and are localised to endogenous R-loops where they act to suppress R-loop formation. Our results place SA proteins on chromatin upstream of the cohesin complex and reveal a role for SA in cohesin loading at R-loops which is independent of NIPBL, the canonical cohesin loader. We propose that SA takes advantage of this structural R-loop platform to link cohesin loading and chromatin structure with diverse genome functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease.Competing Interest StatementThe authors have declared no competing interest.