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Division of Labor between PCNA Loaders in DNA Replication and Sister Chromatid Cohesion Establishment.

Mol Cell. 2020 May 21;78(4):725-738.e4. Epub 2020 Apr 10
Hon Wing Liu 1 , Céline Bouchoux 1 , Mélanie Panarotto 1 , Yasutaka Kakui 1 , Harshil Patel 2 , Frank Uhlmann 3
Hon Wing Liu 1 , Céline Bouchoux 1 , Mélanie Panarotto 1 , Yasutaka Kakui 1 , Harshil Patel 2 , Frank Uhlmann 3
+ et al

[No authors listed]

Author information
  • 1 Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 2 Bioinformatics and Biostatistics Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 3 Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: frank.uhlmann@crick.ac.uk.

摘要


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.

KEYWORDS: Chromosome Segregation, Cohesion Establishment, Ctf18, DNA Replication, Eco1, PCNA, Replication Factor C, Rfc1, S. cerevisiae, Sister Chromatid Cohesion