Schmidt TT~Hombauer H, 2017

Pubmed ID 28416670
Title GLN3 inactivation cause imbalanced dNTP pools and increased mutagenesis.
Authors Tobias T Schmidt, Gloria Reyes, Kerstin Gries, Cemile Ümran Ceylan, Sushma Sharma, Matthias Meurer, Michael Knop, Andrei Chabes, Hans Hombauer
Abstract SHM2) have not been previously associated to the suppression of mutations. Loss of either the transcription factor Gln3 or inactivation of the CTP synthetase Ura7 both resulted in the activation of the DNA damage response and imbalanced dNTP pools. Importantly, these dNTP imbalances are strongly mutagenic in genetic backgrounds where DNA polymerase function or MMR activity is partially compromised. Previous reports have shown that dNTP pool imbalances can be caused by mutations altering the allosteric regulation of enzymes involved in dNTP biosynthesis (e.g., RNR or dCMP deaminase). Here, we provide evidence that mutations affecting genes involved in RNR substrate production can cause dNTP imbalances, which cannot be compensated by RNR or other enzymatic activities. Moreover, Gln3 inactivation links nutrient deprivation to increased mutagenesis. Our results suggest that similar genetic interactions could drive mutator phenotypes in cancer cells.
Citation Proc. Natl. Acad. Sci. U.S.A. 2017; 114:E4442-E4451


Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Schmidt TT~Hombauer H, 2017 mutation frequency (CanR) standard hap a (post-SGA) ~4,800 None
Schmidt TT~Hombauer H, 2017 (lys2-10A) standard hap a (post-SGA) ~4,800 None

Curation history


May 27, 2020 To request.

Tested strains

May 27, 2020 To request.