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

Hon Wing Liu, Céline Bouchoux, Mélanie Panarotto, Yasutaka Kakui, Harshil Patel, Frank Uhlmann

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)725-738.e4
JournalMolecular Cell
Volume78
Issue number4
DOIs
Publication statusPublished - 2020 May 21
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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