journal.pone.0187775.pdf (8.56 MB)
Fission yeast strains with circular chromosomes require the 9-1-1 checkpoint complex for the viability in response to the anti-cancer drug 5-fluorodeoxyuridine
journal contribution
posted on 2023-06-09, 11:43 authored by Jo MurrayThymidine kinase converts 5-fluorodeoxyuridine to 5-fluorodeoxyuridine monophosphate, which causes disruption of deoxynucleotide triphosphate ratios. The fission yeast Schizosaccharomyces pombe does not express endogenous thymidine kinase but 5-fluorodeoxyuridine inhibits growth when exogenous thymidine kinase is expressed. Unexpectedly, we found that 5-fluorodeoxyuridine causes S phase arrest even without thymidine kinase expression. DNA damage checkpoint proteins such as the 9-1-1 complex were required for viability in the presence of 5-fluorodeoxyuridine. We also found that strains with circular chromosomes, due to loss of pot1+, which have higher levels of replication stress, were more sensitive to loss of the 9-1-1 complex in the presence of 5-fluorodeoxyuridine. Thus, our results suggest that strains carrying circular chromosomes exhibit a greater dependence on DNA damage checkpoints to ensure viability in the presence of 5-fluorodeoxyuridine compared to stains that have linear chromosomes.
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Publication status
- Published
File Version
- Published version
Journal
PLoS MedicineISSN
1549-1277Publisher
Public Library of ScienceExternal DOI
Issue
11Volume
12Page range
1-16Article number
e0187775Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-01-23First Open Access (FOA) Date
2018-01-23First Compliant Deposit (FCD) Date
2018-01-23Usage metrics
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