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
|
Resource |
Yeast |
FY18372
FY18394 |