Eukaryotic DNA damage checkpoint activation in response to double-strand breaks |
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Authors: | Karen?Finn Email author" target="_blank">Noel?Francis?LowndesEmail author Email author" target="_blank">Muriel?GrenonEmail author |
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Institution: | (1) Genome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, University Road, Galway, Ireland; |
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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. |
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Keywords: | |
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