Repair of methyl lesions in DNA and RNA by oxidative demethylation.
It was established several decades ago that it is crucial for all organisms to repair their DNA to maintain genome integrity and numerous proteins are dedicated to this purpose. However, it is becoming increasingly clear that it is also important to prevent and repair lesions in the macromolecules encoded by the DNA, i.e. RNA and protein. Many neurological disorders such as Alzheimer's disease and Parkinson's disease are associated with the aggregation of defective, misfolded proteins, and several mechanisms exist to prevent such aggregation, both through direct protein repair and through the elimination and repair of faulty or damaged RNAs. A few years ago, it was discovered that the E. coli AlkB protein represented an iron and 2-oxoglutarate dependent oxygenase capable of repairing methyl lesions in DNA by a novel mechanism, termed oxidative demethylation. Furthermore, it was found that both human and bacterial AlkB proteins were able to demethylate lesions also in RNA, thus representing the first example of RNA repair. In the present review, recent findings on the AlkB mechanism, as well as on RNA damage in general, will be discussed.
Falnes
P Ø
PØ
Department of Molecular Biosciences, University of Oslo, P.O. Box 1041 Blindern, N-0316 Oslo, Norway. pal.falnes@imbv.uio.no
Klungland
A
A
Alseth
I
I
D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics*
D029968:Escherichia coli Proteins; D011687:Purines; D011743:Pyrimidines; D012313:RNA; D004247:DNA; D006899:Mixed Function Oxygenases; C466427:AlkB protein, E coli