RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

Jongchan Yeo, Rena A. Goodman, Nicole T. Schirle, Sheila S. David, Peter A. Beal

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

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 a. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing.

Original languageEnglish (US)
Pages (from-to)20715-20719
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number48
DOIs
StatePublished - Nov 30 2010

Keywords

  • ADAR
  • Base excision repair
  • DNA damage
  • Nucleic acids
  • Oxidative stress

ASJC Scopus subject areas

  • General

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