2003
DOI: 10.1128/ec.2.2.256-264.2003
|View full text |Cite
|
Sign up to set email alerts
|

Novel Small-Molecule Inhibitors of RNA Polymerase III

Abstract: A genetic approach utilizing the yeast Saccharomyces cerevisiae was used to identify the target of antifungal compounds. This analysis led to the identification of small molecule inhibitors of RNA polymerase (Pol) III from Saccharomyces cerevisiae. Three lines of evidence show that UK-118005 inhibits cell growth by targeting RNA Pol III in yeast. First, a dominant mutation in the g domain of Rpo31p, the largest subunit of RNA Pol III, confers resistance to the compound. Second, UK-118005 rapidly inhibits tRNA … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

2
83
1

Year Published

2005
2005
2024
2024

Publication Types

Select...
9
1

Relationship

0
10

Authors

Journals

citations
Cited by 79 publications
(87 citation statements)
references
References 37 publications
2
83
1
Order By: Relevance
“…What our data add to this picture is that a reduction in ternary complex levels can occur as a direct (and perhaps, for cell physiology, the most important) consequence of a decrease in Pol III transcription. Interestingly, a genome expression remodeling reminiscent of the general amino acid control response has recently been observed in response to treatment of yeast cells with a small molecule inhibitor (UK-118005) of RNA Pol III (56). Such a response was also found to be GCN2 independent; however, in disagreement with our observations, GCN4 mRNA translation was not found to be increased in UK-118005-treated cells.…”
Section: Discussioncontrasting
confidence: 57%
“…What our data add to this picture is that a reduction in ternary complex levels can occur as a direct (and perhaps, for cell physiology, the most important) consequence of a decrease in Pol III transcription. Interestingly, a genome expression remodeling reminiscent of the general amino acid control response has recently been observed in response to treatment of yeast cells with a small molecule inhibitor (UK-118005) of RNA Pol III (56). Such a response was also found to be GCN2 independent; however, in disagreement with our observations, GCN4 mRNA translation was not found to be increased in UK-118005-treated cells.…”
Section: Discussioncontrasting
confidence: 57%
“…For the polymerase III inhibition experiments, the medium was removed from the cells 10 h before time point 0 and mixed with either DMSO (Hybri-Max; Sigma) or ML60218 (Calbiochem catalog no. 557403) at a final concentration of 20 M (10 mM stock dissolved in DMSO) (45) and readded to the cells at 2 ml per well.…”
Section: Methodsmentioning
confidence: 99%
“…First, we used ML-60218, an indazolo-sulfonamide compound that specifically inhibits RNA polymerase III (Wu et al 2003). ML-60218 does not completely inhibit tRNA synthesis, but a leakiness of 20%-30% is expected (Iwasaki et al 2010).…”
Section: Inhibition Of Trna Synthesis Stalls 2-thiolation At Elevatedmentioning
confidence: 99%