Preparation for DNA Replication: The Key to a Successful S Phase

FEBS Lett. 2019 Oct;593(20):2853-2867. doi: 10.1002/1873-3468.13619. Epub 2019 Oct 15.

Abstract

Successful genome duplication is required for cell proliferation and demands extraordinary precision and accuracy. The mechanisms by which cells enter, progress through, and exit S phase are intense areas of focus in the cell cycle and genome stability fields. Key molecular events in the G1 phase of the cell division cycle, especially origin licensing, are essential for pre-establishing conditions for efficient DNA replication during the subsequent S phase. If G1 events are poorly regulated or disordered, then DNA replication can be compromised leading to genome instability, a hallmark of tumorigenesis. Upon entry into S phase, coordinated origin firing and replication progression ensure complete, timely, and precise chromosome replication. Both G1 and S phase progressions are controlled by master cell cycle protein kinases and ubiquitin ligases that govern the activity and abundance of DNA replication factors. In this short review, we describe current understanding and recent developments related to G1 progression and S phase entrance and exit with a particular focus on origin licensing regulation in vertebrates.

Keywords: DNA replication; cell cycle; checkpoint; genome stability; origin licensing; replication stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle / genetics
  • Cell Cycle Checkpoints / genetics
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • DNA Replication*
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • G1 Phase / genetics*
  • Gene Expression Regulation
  • Genome*
  • Genomic Instability
  • Humans
  • S Phase / genetics*
  • Signal Transduction
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Ubiquitin-Protein Ligases
  • Cyclin-Dependent Kinases