RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1.
Editing of the pre-mRNA for the DNA repair enzyme NEIL1 causes a lysine to arginine change in the lesion recognition loop of the protein. The two forms of NEIL1 are shown here to have distinct enzymatic properties. The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. In addition, we show that the NEIL1 recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. The edited adenosine resides in an A-C mismatch in a hairpin stem formed by pairing of exon 6 to the immediate upstream intron 5 sequence. As expected for an ADAR1 site, editing at this position is increased in human cells treated with interferon α. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing.
Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
Jongchan
J
Yeo
Rena A
RA
Goodman
Nicole T
NT
Schirle
Sheila S
SS
David
Peter A
PA
Beal
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics*; D045647:DNA Glycosylases / Q000737:chemistry / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009690:Nucleic Acid Conformation / Q000187:drug effects; D017393:RNA Editing / Q000187:drug effects / Q000235:genetics*; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects
D016898:Interferon-alpha; D012322:RNA Precursors; D045647:DNA Glycosylases; C473634:NEIL1 protein, human; D045643:DNA Repair Enzymes