Multiple roles of Pol epsilon in eukaryotic chromosome replication

Milos A Cvetkovic; Esther Ortega; Roberto Bellelli; Alessandro Costa

doi:10.1042/BST20210082

Multiple roles of Pol epsilon in eukaryotic chromosome replication

Biochem Soc Trans. 2022 Feb 28;50(1):309-320. doi: 10.1042/BST20210082.

Authors

Milos A Cvetkovic¹, Esther Ortega^{1

2}, Roberto Bellelli³, Alessandro Costa¹

Affiliations

¹ Macromolecular Machines Laboratory, The Francis Crick Institute, London NW1 1AT, U.K.
² Department of Macromolecular Structures, Spanish National Centre for Biotechnology, 28049 Madrid, Spain.
³ Centre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, U.K.

Abstract

Pol epsilon is a tetrameric assembly that plays distinct roles during eukaryotic chromosome replication. It catalyses leading strand DNA synthesis; yet this function is dispensable for viability. Its non-catalytic domains instead play an essential role in the assembly of the active replicative helicase and origin activation, while non-essential histone-fold subunits serve a critical function in parental histone redeposition onto newly synthesised DNA. Furthermore, Pol epsilon plays a structural role in linking the RFC-Ctf18 clamp loader to the replisome, supporting processive DNA synthesis, DNA damage response signalling as well as sister chromatid cohesion. In this minireview, we discuss recent biochemical and structural work that begins to explain various aspects of eukaryotic chromosome replication, with a focus on the multiple roles of Pol epsilon in this process.

Keywords: CMG; Ctf18; Pol epsilon; chromatin; cryo-EM; replisome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromosomes / metabolism
DNA / genetics
DNA Polymerase II / metabolism
DNA Replication
Histones / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins* / metabolism

Substances

Histones
Saccharomyces cerevisiae Proteins
DNA
DNA Polymerase II