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PMID: 21068368 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 48 ·2010-11-30 ·Pages 20715-9

Yeo J, Goodman RA, Schirle NT, David SS, Beal PA

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

MeSH Terms
Amino Acid Sequence Amino Acid Substitution/genetics Base Sequence Cell Line, Tumor DNA Damage/genetics DNA Glycosylases/chemistry,metabolism DNA Repair Enzymes/chemistry,metabolism Humans Interferon-alpha/pharmacology Kinetics Molecular Sequence Data Mutation/genetics Nucleic Acid Conformation/drug effects RNA Editing/drug effects,genetics RNA Precursors/chemistry,genetics,metabolism Substrate Specificity/drug effects
Chemicals
Interferon-alpha RNA Precursors DNA Glycosylases NEIL1 protein, human DNA Repair Enzymes
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yeo Jongchan
Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
Goodman Rena A
Schirle Nicole T
David Sheila S
Beal Peter A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1009231107
Published
2010-11-30
Epub
2010-00-10
Pages
20715-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2996456
Subset
IM
Grants
NIGMS NIH HHS · T32-GM08799 · United States
NIGMS NIH HHS · T32 GM008799 · United States
NCI NIH HHS · R01-CA090689 · United States
NIGMS NIH HHS · R01-GM061115 · United States
NIGMS NIH HHS · R01 GM061115 · United States
NCI NIH HHS · R01 CA090689 · United States
External Links
PubMed source DOI: 10.1073/pnas.1009231107 PMC Full Text View journal details
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