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Division of labor between PCNA loaders in DNA replication and sister chromatid cohesion establishment.

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journal contribution
posted on 25.06.2020, 13:55 by Hon Wing Liu, Céline Bouchoux, Mélanie Panarotto, Yasutaka Kakui, Harshil Patel, Frank Uhlmann
Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Several replication-fork-associated "cohesion establishment factors," including the multifunctional Ctf18-RFC complex, aid this process in as yet unknown ways. Here, we show that Ctf18-RFC's role in sister chromatid cohesion correlates with PCNA loading but is separable from its role in the replication checkpoint. Ctf18-RFC loads PCNA with a slight preference for the leading strand, which is dispensable for DNA replication. Conversely, the canonical Rfc1-RFC complex preferentially loads PCNA onto the lagging strand, which is crucial for DNA replication but dispensable for sister chromatid cohesion. The downstream effector of Ctf18-RFC is cohesin acetylation, which we place toward a late step during replication maturation. Our results suggest that Ctf18-RFC enriches and balances PCNA levels at the replication fork, beyond the needs of DNA replication, to promote establishment of sister chromatid cohesion and possibly other post-replicative processes.


Crick (Grant ID: 10198, Grant title: Uhlmann FC001198) European Research Council (Grant ID: 670412 - ChromatidCohesion, Grant title: ERC 670412 - ChromatidCohesion)