Eukaryotic DNA damage checkpoint activation in response to double-strand breaks

Cell Mol Life Sci. 2012 May;69(9):1447-73. doi: 10.1007/s00018-011-0875-3. Epub 2011 Nov 15.

Abstract

Double-strand breaks (DSBs) are the most detrimental form of DNA damage. Failure to repair these cytotoxic lesions can result in genome rearrangements conducive to the development of many diseases, including cancer. The DNA damage response (DDR) ensures the rapid detection and repair of DSBs in order to maintain genome integrity. Central to the DDR are the DNA damage checkpoints. When activated by DNA damage, these sophisticated surveillance mechanisms induce transient cell cycle arrests, allowing sufficient time for DNA repair. Since the term "checkpoint" was coined over 20 years ago, our understanding of the molecular mechanisms governing the DNA damage checkpoint has advanced significantly. These pathways are highly conserved from yeast to humans. Thus, significant findings in yeast may be extrapolated to vertebrates, greatly facilitating the molecular dissection of these complex regulatory networks. This review focuses on the cellular response to DSBs in Saccharomyces cerevisiae, providing a comprehensive overview of how these signalling pathways function to orchestrate the cellular response to DNA damage and preserve genome stability in eukaryotic cells.

Publication types

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

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Cycle Checkpoints / physiology
  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2
  • DNA Breaks, Double-Stranded*
  • DNA Damage / genetics*
  • DNA Damage / physiology*
  • Eukaryota / cytology
  • Eukaryota / genetics
  • Eukaryota / metabolism
  • Genomic Instability
  • Humans
  • Models, Biological
  • Models, Genetic
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction / genetics

Substances

  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • rad9 protein
  • Protein Kinases
  • Checkpoint Kinase 2
  • Checkpoint Kinase 1
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae