Home Blog of Signal Transduction Others DNA/RNA Synthesis Loss of tRNA methyltransferase 9 and DNA damage response genes in yeast confers sensitivity to aminoglycosides

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Loss of tRNA methyltransferase 9 and DNA damage response genes in yeast confers sensitivity to aminoglycosides

tRNA methyltransferase 9 (Trm9)-catalysed tRNA modifications have been shown to translationally enhance the DNA damage response (DDR). Here, we show that Saccharomyces cerevisiae trm9Δ and distinct DNA repair and spindle assembly checkpoint (SAC) mutants are differentially sensitive to the aminoglycosides tobramycin, gentamicin and amikacin, indicating DDR and SAC activation might rely on translation fidelity, under aminoglycoside stress. Further, we report that the DNA damage induced by aminoglycosides in the base excision repair mutants ogg1Δ and apn1Δ is mediated by reactive oxygen species, which induce the DNA adduct 8-hydroxy deoxyguanosine. Finally, the synergistic effect of tobramycin and the DNA damaging agent bleomycin to sensitize trm9Δ and the DDR mutants mlh1Δ, rad51Δ, mre11Δ and sgs1Δ at significantly lower concentrations compared to wild-type suggests that cells with tRNA modification dysregulation and DNA repair gene defects can be selectively sensitized using a combination of translation inhibitors and DNA damaging agents.

 

Comments：

The study shows that tRNA methyltransferase 9 (Trm9) is important for translation enhancement in the DNA damage response (DDR) and sensitivity to aminoglycosides, with a synergistic effect observed in cells with tRNA modification dysregulation and DNA repair gene defects when exposed to translation inhibitors and DNA damaging agents.

Related Products

Cat.No. Product Name Information
S1214 Bleomycin sulfate Bleomycin sulfate is a glycopeptide antibiotic and a DNA synthesis inhibitor, as well as an anticancer agent for squamous cell carcinomas (SCC) with an IC50 of 4 nM in UT-SCC-19A cells. Bleomycin sulfate is a DNA synthesis inhibitor.

Related Targets

DNA/RNA Synthesis Antineoplastic and Immunosuppressive Antibiotics Selection Antibiotics for Transfected Cell