RRC ID 49560
Author Shamim HM, Minami Y, Tanaka D, Ukimori S, Murray JM, Ueno M.
Title 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 PLoS One
Abstract Thymidine 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.
Volume 12(11)
Pages e0187775
Published 2017-11-9
DOI 10.1371/journal.pone.0187775
PII PONE-D-17-16192
PMID 29121084
PMC PMC5679574
MeSH Antineoplastic Agents / pharmacology* Chromosome Segregation / drug effects Chromosomes, Fungal / genetics* DNA Damage DNA Replication / drug effects DNA, Fungal / genetics* Floxuridine / pharmacology* Microbial Viability / drug effects* Mutation Mycoses S Phase Cell Cycle Checkpoints / drug effects S Phase Cell Cycle Checkpoints / genetics Schizosaccharomyces / cytology Schizosaccharomyces / drug effects Schizosaccharomyces / genetics* Schizosaccharomyces / physiology* Schizosaccharomyces pombe Proteins / genetics Species Specificity Telomere / genetics
IF 2.74
Times Cited 0
Yeast FY18372 FY18394