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PMID: 6093094 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

In vivo mutagenesis by O6-methylguanine built into a unique site in a viral genome.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 81 ·No. 20 ·1984-10-00 ·Pages 6271-5

Loechler EL, Green CL, Essigmann JM

Abstract

The mutagenicity of O6-methylguanine (O6MeGua), a chemical carcinogen-DNA adduct, has been studied in vivo by using a single-stranded M13mp8 genome in which a single O6MeGua residue was positioned in the unique recognition site for the restriction endonuclease Pst I. Transformation of Escherichia coli MM294A cells with this vector gave progeny phage, of which 0.4% were mutated in their Pst I site. In a separate experiment, cellular levels of O6MeGua-DNA methyltransferase (an O6MeGua-repair protein) were depleted by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) prior to viral DNA uptake. In these cells, the mutation frequency due to O6MeGua increased with increasing MNNG dose (the highest mutation frequency observed was 20%). DNA sequence analysis of 60 mutant genomes revealed that O6MeGua induced exclusively G-to-A transitions.

MeSH Terms
Coliphages/genetics DNA Repair DNA, Viral/genetics Escherichia coli/genetics Genetic Vectors Guanine/analogs & derivatives Mutation
Chemicals
DNA, Viral Guanine O-(6)-methylguanine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Loechler E L
Green C L
Essigmann J M
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20 references, click to expand
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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
0027-8424
DOI
10.1073/pnas.81.20.6271
Published
1984-10-00
Pages
6271-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC391905
Subset
IM
Grants
NIEHS NIH HHS · 5 PO1 ES00597 · United States
NCI NIH HHS · CA 33821 · United States
NIEHS NIH HHS · T 32 ES07020 · United States
External Links
PubMed source DOI: 10.1073/pnas.81.20.6271 PMC Full Text View journal details
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