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Cited by 210

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Human AlkB Homolog ABH8 Is a tRNA Methyltransferase Required for Wobble Uridine Modification and DNA Damage Survival

Open access
Fu, Dragony, Brophy, Jennifer A. N., Chan, Clement T. Y., Atmore, Kyle A., Begley, Ulrike, Paules, Richard S., Dedon, Peter C., Begley, Thomas J., Samson, Leona D.·2010·Molecular and Cellular Biology

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.

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Metadata

Authors
Fu, D., Brophy, J. A. N., Chan, C. T. Y., Atmore, K. A., Begley, U., Paules, R. S., Dedon, P. C., Begley, T. J., & Samson, L. D.
Venue
Molecular and Cellular Biology
Published
2010-05-01
Volume
30
Issue
10
Pages
2449-2459
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2150038630
Cited by
210
References
4
FWCI
5.20
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Human AlkB Homolog ABH8 Is a tRNA Methyltransferase Required for Wobble Uridine Modification and DNA Damage Survival. https://app.cochat.ai/papers/10.1128/mcb.01604-09
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Fu, D., Brophy, J. A. N., Chan, C. T. Y., Atmore, K. A., Begley, U., Paules, R. S., Dedon, P. C., Begley, T. J., & Samson, L. D. (2010). Human AlkB Homolog ABH8 Is a tRNA Methyltransferase Required for Wobble Uridine Modification and DNA Damage Survival. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.01604-09

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