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Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA

Author

Listed:
  • Per Arne Aas

    (Norwegian University of Science and Technology)

  • Marit Otterlei

    (Norwegian University of Science and Technology)

  • Pål Ø. Falnes

    (University of Oslo, The National Hospital)

  • Cathrine B. Vågbø

    (Norwegian University of Science and Technology)

  • Frank Skorpen

    (Norwegian University of Science and Technology)

  • Mansour Akbari

    (Norwegian University of Science and Technology)

  • Ottar Sundheim

    (Norwegian University of Science and Technology)

  • Magnar Bjørås

    (University of Oslo, The National Hospital)

  • Geir Slupphaug

    (Norwegian University of Science and Technology)

  • Erling Seeberg

    (University of Oslo, The National Hospital)

  • Hans E. Krokan

    (Norwegian University of Science and Technology)

Abstract

Repair of DNA damage is essential for maintaining genome integrity, and repair deficiencies in mammals are associated with cancer, neurological disease and developmental defects1. Alkylation damage in DNA is repaired by at least three different mechanisms, including damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine by Escherichia coli AlkB2,3. By contrast, little is known about consequences and cellular handling of alkylation damage to RNA4. Here we show that two human AlkB homologues, hABH2 and hABH3, also are oxidative DNA demethylases and that AlkB and hABH3, but not hABH2, also repair RNA. Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. In addition, AlkB and hABH3 expressed in E. coli reactivate methylated RNA bacteriophage MS2 in vivo, illustrating the biological relevance of this repair activity and establishing RNA repair as a potentially important defence mechanism in living cells. The different catalytic properties and the different subnuclear localization patterns shown by the human homologues indicate that hABH2 and hABH3 have distinct roles in the cellular response to alkylation damage.

Suggested Citation

  • Per Arne Aas & Marit Otterlei & Pål Ø. Falnes & Cathrine B. Vågbø & Frank Skorpen & Mansour Akbari & Ottar Sundheim & Magnar Bjørås & Geir Slupphaug & Erling Seeberg & Hans E. Krokan, 2003. "Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA," Nature, Nature, vol. 421(6925), pages 859-863, February.
    • Handle: RePEc:nat:nature:v:421:y:2003:i:6925:d:10.1038_nature01363
    DOI: 10.1038/nature01363
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    Cited by:

    1. Junqiao Jia & Tarek Hilal & Katherine E. Bohnsack & Aleksandar Chernev & Ning Tsao & Juliane Bethmann & Aruna Arumugam & Lane Parmely & Nicole Holton & Bernhard Loll & Nima Mosammaparast & Markus T. B, 2023. "Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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