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PMID: 7659512 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

8-Hydroxyadenine (7,8-dihydro-8-oxoadenine) induces misincorporation in in vitro DNA synthesis and mutations in NIH 3T3 cells.

Nucleic acids research ·Vol. 23 ·No. 15 ·1995-08-11 ·Pages 2893-9

Kamiya H, Miura H, Murata-Kamiya N, Ishikawa H, Sakaguchi T, Inoue H, Sasaki T, Masutani C, Hanaoka F, Nishimura S

Abstract

An oligodeoxyribonucleotide containing 8-hydroxyadenine (OH8Ade) was chemically synthesized and single- and double-stranded c-Ha-ras gene fragments with OH8Ade at the second position of codon 61 were prepared. The single-stranded ras gene fragment was used as a template for in vitro DNA synthesis with the Klenow fragment of Escherichia coli DNA polymerase I, Taq DNA polymerase, rat DNA polymerase beta and mouse DNA polymerase alpha. The former two enzymes exclusively incorporated dTMP opposite OH8Ade. The DNA polymerases alpha and beta misinserted dGMP, and dAMP and dGMP, respectively. The c-Ha-ras gene was constructed using the double-stranded ras gene fragment containing OH8Ade and was transfected into NIH 3T3 cells. The gene with OH8Ade induced focus formation, indicating that OH8Ade elicited point mutations in cells. When c-Ha-ras genes present in transformed cells were analyzed, an A-->G transition and an A-->C transversion were detected. These results indicate that OH8Ade induced misincorporation in in vitro DNA synthesis and mutations in mammalian cells.

MeSH Terms
3T3 Cells Adenine/analogs & derivatives,chemical synthesis Amino Acid Sequence Animals Base Sequence DNA/biosynthesis DNA Damage/genetics DNA Mutational Analysis DNA, Single-Stranded/metabolism DNA-Directed DNA Polymerase/metabolism Escherichia coli/enzymology Genes, ras/genetics Mice Molecular Sequence Data Mutagens Polydeoxyribonucleotides/chemical synthesis Rats Templates, Genetic Transfection
Chemicals
DNA, Single-Stranded Mutagens Polydeoxyribonucleotides 8-hydroxyadenine DNA DNA-Directed DNA Polymerase Adenine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kamiya H
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Miura H
Murata-Kamiya N
Ishikawa H
Sakaguchi T
Inoue H
Sasaki T
Masutani C
Hanaoka F
Nishimura S
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/23.15.2893
Published
1995-08-11
Pages
2893-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC307127
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/23.15.2893 PMC Full Text View journal details
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