@article{1e23ecf7ee3b45349caffc41e992be2c,
title = "Division of Labor between PCNA Loaders in DNA Replication and Sister Chromatid Cohesion Establishment",
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.",
keywords = "Chromosome Segregation, Cohesion Establishment, Ctf18, DNA Replication, Eco1, PCNA, Replication Factor C, Rfc1, S. cerevisiae, Sister Chromatid Cohesion",
author = "Liu, {Hon Wing} and C{\'e}line Bouchoux and M{\'e}lanie Panarotto and Yasutaka Kakui and Harshil Patel and Frank Uhlmann",
note = "Funding Information: We are indebted to Chuanhe Yu, Hui Zhou, and Zhiguo Zhang for their advice on eSPAN and for the PCNA antibody, as well as to the Francis Crick Institute Advanced Sequencing Science Technology Platform. We would like to thank John Diffley and members of our laboratory for discussions and comments on the manuscript. This project received funding from the European Research Council (ERC) under the Horizon 2020 program (grant agreement No. 670412) and The Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001198), the UK Medical Research Council (FC001198), and the Wellcome Trust (FC001198). H.W.L. and F.U. conceived the study. H.W.L. performed all experiments apart from the analyses in Figure 7 that were performed by C.B. M.P. helped with the Pol30C81R experiments. Y.K. contributed the microarray data analyses, and H.P. performed the eSPAN data analyses. H.W.L. and F.U. wrote the manuscript with input from all authors. The authors declare no competing interests. Funding Information: We are indebted to Chuanhe Yu, Hui Zhou, and Zhiguo Zhang for their advice on eSPAN and for the PCNA antibody, as well as to the Francis Crick Institute Advanced Sequencing Science Technology Platform. We would like to thank John Diffley and members of our laboratory for discussions and comments on the manuscript. This project received funding from the European Research Council (ERC) under the Horizon 2020 program (grant agreement No. 670412 ) and The Francis Crick Institute , which receives its core funding from Cancer Research UK ( FC001198 ), the UK Medical Research Council ( FC001198 ), and the Wellcome Trust ( FC001198 ). Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = may,
day = "21",
doi = "10.1016/j.molcel.2020.03.017",
language = "English",
volume = "78",
pages = "725--738.e4",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",
}