Misincorporation of dAMP opposite 2-hydroxyadenine, an oxidative form of adenine.

Abstract:

:Nucleotide incorporation opposite an oxidative form of adenine, 2-hydroxyadenine (2-OH-Ade) was investigated. When a primed template with 2-OH-Ade was treated with an exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I (KFexo-), recombinant rat DNA polymerase beta (pol beta) or calf thymus DNA polymerase alpha (pol alpha), incorporation of dTMP and dAMP was observed. In addition, KFexo- inserted dGMP as well. A steady-state kinetic study indicated that the insertion of dAMP and dTMP opposite the DNA lesion occurred with similar frequency with KFexo- and pol beta. Insertion of dTMP opposite 2-OH-Ade was favored to that of dAMP by pol alpha. Chain extension from the A.2-OH-Ade pair is less favored than that from the T.2-OH-Ade pair by all three DNA polymerase. Analysis of full-length products of in vitro DNA synthesis showed that dTMP and dAMP were incorporated by DNA polymerases and that exonuclease-proficient and -deficient Klenow fragments also inserted dGMP opposite 2-OH-Ade. These results suggest that formation of 2-OH-Ade from A in DNA will induce A-->T and A-->C transversions in cells.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Kamiya H,Ueda T,Ohgi T,Matsukage A,Kasai H

doi

10.1093/nar/23.5.761

subject

Has Abstract

pub_date

1995-03-11 00:00:00

pages

761-6

issue

5

eissn

0305-1048

issn

1362-4962

pii

4w0224

journal_volume

23

pub_type

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