Topoisomerases promote replication fork pausing at proteinaceous barriers

Living organisms have to faithfully duplicate all the DNA in their chromosomes once and only once during every cell division. Replication forks pause/slow/arrest/stall during progression through chromosomes at certain tight DNA/protein complexes known as Replication Fork Barriers (RFB).  This pausing is promoted by the Fork Pausing Complex (FPC, composed of the Tof1 and Csm3 proteins in budding yeast) and opposed by Rrm3 helicase, a motor-like protein believed to displace obstacles.

Maksym Shyian and collaborators in the Shore laboratory have now discovered that the Tof1-Csm3 complex promotes fork pausing independently of Rrm3 helicase, in contrast to an old model. Instead the Fork Pausing Complex was found to mediate topoisomerase I (Top1) association with the replisome, which, together with Top2, is essential for fork slowdown (replisome sTOP mechanism).

The study was published in Genes & Development on December 5, 2019.

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