Review

Cellular and Molecular Life Sciences

, Volume 69, Issue 9, pp 1447-1473

First online:

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

  • Karen FinnAffiliated withGenome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway
  • , Noel Francis LowndesAffiliated withGenome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway Email author 
  • , Muriel GrenonAffiliated withGenome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.

Keywords

Cancer Checkpoint DNA damage Double-strand break Yeast Genome instability