Gene Set: FU_INTERACT_WITH_ALKBH8

Standard name FU_INTERACT_WITH_ALKBH8
Systematic name M2478
Brief description 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 gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 20308323   Authors: Fu D,Brophy JA,Chan CT,Atmore KA,Begley U,Paules RS,Dedon PC,Begley TJ,Samson LD
Exact source Table 2
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Human_NCBI_Gene_ID
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Version history 3.1: First introduced

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