Proteins identified by mass spectrometry in complexes containing ALKBH8 [GeneID=91801].
Full description or abstract
tRNA nucleosides are extensively modified to ensure their proper function in translation. However, many of the enzymes responsible for tRNA modifications in mammals await identification. Here, we show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm(5)U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival. We find that ABH8 interacts specifically with tRNAs containing mcm(5)U and that purified ABH8 complexes methylate RNA in vitro. Significantly, ABH8 depletion in human cells reduces endogenous levels of mcm(5)U in RNA and increases cellular sensitivity to DNA-damaging agents. Moreover, DNA-damaging agents induce ABH8 expression in an ATM-dependent manner. These results expand the role of mammalian AlkB proteins beyond that of direct DNA repair and support a regulatory mechanism in the DNA damage response pathway involving modulation of tRNA modification.
Collection
C2: Curated CGP: Chemical and Genetic Perturbations
Creative Commons Attribution 4.0 International License (CC-BY-4.0)
The contents of this gene set are protected by copyright (c) 2004-2026 Broad Institute, Inc., Massachusetts Institute of Technology,
and Regents of the University of California, subject to the terms and conditions of the
Creative Commons Attribution 4.0 International License.
