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Genetics. 2013 Jan;193(1):143-57. doi: 10.1534/genetics.112.145730. Epub 2012 Nov 12.

A mammalian-like DNA damage response of fission yeast to nucleoside analogs.

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  • 1Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.

Abstract

Nucleoside analogs are frequently used to label newly synthesized DNA. These analogs are toxic in many cells, with the exception of the budding yeast. We show that Schizosaccharomyces pombe behaves similarly to metazoans in response to analogs 5-bromo-2'-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU). Incorporation causes DNA damage that activates the damage checkpoint kinase Chk1 and sensitizes cells to UV light and other DNA-damaging drugs. Replication checkpoint mutant cds1Δ shows increased DNA damage response after exposure. Finally, we demonstrate that the response to BrdU is influenced by the ribonucleotide reductase inhibitor, Spd1, suggesting that BrdU causes dNTP pool imbalance in fission yeast, as in metazoans. Consistent with this, we show that excess thymidine induces G1 arrest in wild-type fission yeast expressing thymidine kinase. Thus, fission yeast responds to nucleoside analogs similarly to mammalian cells, which has implications for their use in replication and damage research, as well as for dNTP metabolism.

PMID:
23150603
[PubMed - indexed for MEDLINE]
PMCID:
PMC3527242
Free PMC Article
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