Replication-Coupled DNA Repair

Mol Cell. 2019 Jun 6;74(5):866-876. doi: 10.1016/j.molcel.2019.04.027.

Abstract

The replisome quickly and accurately copies billions of DNA bases each cell division cycle. However, it can make errors, especially when the template DNA is damaged. In these cases, replication-coupled repair mechanisms remove the mistake or repair the template lesions to ensure high fidelity and complete copying of the genome. Failures in these genome maintenance activities generate mutations, rearrangements, and chromosome segregation problems that cause many human diseases. In this review, I provide a broad overview of replication-coupled repair pathways, explaining how they fix polymerase mistakes, respond to template damage that acts as obstacles to the replisome, deal with broken forks, and impact human health and disease.

Keywords: DNA damage; DNA replication; break-induced replication; cancer; crosslink repair; excision repair; fork protection; fork reversal; mismatch repair; replication stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Cycle / genetics
  • Chromosome Segregation / genetics
  • DNA Damage / genetics
  • DNA Repair / genetics*
  • DNA Replication / genetics*
  • Genetic Diseases, Inborn / genetics*
  • Genome, Human / genetics*
  • Genomic Instability / genetics
  • Humans
  • Mutation / genetics