The Francis Crick Institute
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Replisome-cohesin interactions provided by the Tof1-Csm3 and Mrc1 cohesion establishment factors.

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journal contribution
posted on 2023-06-08, 12:56 authored by Sudikchya Shrestha, Masashi Minamino, Zhuo A Chen, Céline Bouchoux, Juri Rappsilber, Frank Uhlmann
The chromosomal cohesin complex establishes sister chromatid cohesion during S phase, which forms the basis for faithful segregation of DNA replication products during cell divisions. Cohesion establishment is defective in the absence of either of three non-essential Saccharomyces cerevisiae replication fork components Tof1-Csm3 and Mrc1. Here, we investigate how these conserved factors contribute to cohesion establishment. Tof1-Csm3 and Mrc1 serve known roles during DNA replication, including replication checkpoint signaling, securing replication fork speed, as well as recruiting topoisomerase I and the histone chaperone FACT. By modulating each of these functions independently, we rule out that one of these known replication roles explains the contribution of Tof1-Csm3 and Mrc1 to cohesion establishment. Instead, using purified components, we reveal direct and multipronged protein interactions of Tof1-Csm3 and Mrc1 with the cohesin complex. Our findings open the possibility that a series of physical interactions between replication fork components and cohesin facilitate successful establishment of sister chromatid cohesion during DNA replication.


Crick (Grant ID: CC2137, Grant title: Uhlmann CC2137) Wellcome Trust (Grant ID: 220244/Z/20/Z, Grant title: WT 220244/Z/20/Z)