DNA polymerase ε relies on a unique domain for efficient replisome assembly and strand synthesis. Academic Article uri icon

Overview

abstract

  • DNA polymerase epsilon (Pol ε) is required for genome duplication and tumor suppression. It supports both replisome assembly and leading strand synthesis; however, the underlying mechanisms remain to be elucidated. Here we report that a conserved domain within the Pol ε catalytic core influences both of these replication steps in budding yeast. Modeling cancer-associated mutations in this domain reveals its unexpected effect on incorporating Pol ε into the four-member pre-loading complex during replisome assembly. In addition, genetic and biochemical data suggest that the examined domain supports Pol ε catalytic activity and symmetric movement of replication forks. Contrary to previously characterized Pol ε cancer variants, the examined mutants cause genome hyper-rearrangement rather than hyper-mutation. Our work thus suggests a role of the Pol ε catalytic core in replisome formation, a reliance of Pol ε strand synthesis on a unique domain, and a potential tumor-suppressive effect of Pol ε in curbing genome re-arrangements.

publication date

  • May 15, 2020

Research

keywords

  • DNA Polymerase II
  • DNA Replication
  • Gene Expression Regulation
  • Poly-ADP-Ribose Binding Proteins

Identity

PubMed Central ID

  • PMC7228970

Scopus Document Identifier

  • 85084834194

Digital Object Identifier (DOI)

  • 10.1002/yea.3080

PubMed ID

  • 32415104

Additional Document Info

volume

  • 11

issue

  • 1