RT Journal Article SR Electronic T1 Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.09.23.509019 DO 10.1101/2022.09.23.509019 A1 Nagasaka, Kota A1 Davidson, Iain F. A1 Stocsits, Roman R. A1 Tang, Wen A1 Wutz, Gordana A1 Betty, Paul A1 Panarotto, Melanie A1 Litos, Gabriele A1 Schleiffer, Alexander A1 Gerlich, Daniel Wolfram A1 Peters, Jan-Michael YR 2022 UL http://biorxiv.org/content/early/2022/09/23/2022.09.23.509019.abstract AB Cohesin connects CTCF binding sites and other genomic loci in cis to form chromatin loops, and replicated DNA molecules in trans to mediate sister chromatid cohesion. Whether cohesin uses distinct or related mechanisms to perform these functions is unknown. Here we describe a cohesin hinge mutant, which can extrude DNA into loops but is unable to mediate cohesion. Our results suggest that the latter defect arises during cohesion establishment. The observation that cohesin’s cohesion and loop extrusion activities can be separated indicates that cohesin uses distinct mechanisms to perform these two functions. Unexpectedly, the same hinge mutant can also not be stopped by CTCF boundaries as well as wildtype cohesin. This suggests that cohesion establishment and cohesin’s interaction with CTCF boundaries depend on related mechanisms and raises the possibility that both require transient hinge opening to entrap DNA inside the cohesin ring.Competing Interest StatementThe authors have declared no competing interest.