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

• Published in: Molecular cell Vol. 78; no. 4; pp. 725 - 738.e4
• Main Authors: Liu, Hon Wing, Bouchoux, Céline, Panarotto, Mélanie, Kakui, Yasutaka, Patel, Harshil, Uhlmann, Frank
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-05-2020; Cell Press
• Subjects: Acetyltransferases - genetics; Acetyltransferases - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromatids - physiology; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosome Segregation; Chromosomes, Fungal - physiology; Cohesins; Cohesion Establishment; Ctf18; DNA Replication; Eco1; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; PCNA; Proliferating Cell Nuclear Antigen - genetics; Proliferating Cell Nuclear Antigen - metabolism; Replication Factor C; Replication Protein C - genetics; Replication Protein C - metabolism; Rfc1; S. cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sister Chromatid Cohesion; Eco1; Chromosome Segregation; PCNA; Rfc1; S. cerevisiae; Sister Chromatid Cohesion; DNA Replication; Ctf18; Replication Factor C; Cohesion Establishment
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2020.03.017

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.
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•Distinct roles of Ctf18- and Rfc1-RFC in cohesion establishment and DNA replication•Ctf18-RFC balances PCNA levels between leading and lagging strands•PCNA levels correlate with cohesion establishment•PCNA recruits Eco1 toward a late step during replication maturation
The PCNA sliding clamp plays multiple roles during DNA replication. Here, Liu et al. report that Ctf18-RFC supplies additional PCNA at replication forks, beyond the needs of DNA replication, balancing PCNA levels between leading and lagging strands. This serves an important role during the establishment of sister chromatid cohesion.