Benzo[a]pyrene-derived DNA lesions decrease DNA methylation by murine methyltransferase DNMT3A2

O. V. Lukashevich; N. A. Cherepanova; A. Kolbanovsky; N. E. Geacintov; E. S. Gromova

doi:10.3103/S0027131414020059

Benzo[a]pyrene-derived DNA lesions decrease DNA methylation by murine methyltransferase DNMT3A2

O. V. Lukashevich, N. A. Cherepanova, A. Kolbanovsky, N. E. Geacintov, E. S. Gromova

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

We have studied the impact of DNA damage by one of the most common carcinogens, benzo[a]pyrene, on the functioning of the truncated isoform of DNA methyltransferase Dnmt3a (Dnmt3a2). It is revealed with 30-mer model DNA substrates that DNA methylation rates are drastically reduced when the lesions disturb the structure of the Dnmt3a recognition site or hinder the interaction of the enzyme catalytic loop with the DNA minor groove. Under the chosen conditions, the PWWP domain of Dnmt3a possessing lower affinity to DNA in comparison with the catalytic domain does not influence catalysis.

Original language	English (US)
Pages (from-to)	92-96
Number of pages	5
Journal	Moscow University Chemistry Bulletin
Volume	69
Issue number	2
DOIs	https://doi.org/10.3103/S0027131414020059
State	Published - Mar 2014

Keywords

DNA damage
DNA methyltransferase
benzo[a]pyrene
intercalation
methylation
minor groove

ASJC Scopus subject areas

General Chemistry

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10.3103/S0027131414020059

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title = "Benzo[a]pyrene-derived DNA lesions decrease DNA methylation by murine methyltransferase DNMT3A2",

abstract = "We have studied the impact of DNA damage by one of the most common carcinogens, benzo[a]pyrene, on the functioning of the truncated isoform of DNA methyltransferase Dnmt3a (Dnmt3a2). It is revealed with 30-mer model DNA substrates that DNA methylation rates are drastically reduced when the lesions disturb the structure of the Dnmt3a recognition site or hinder the interaction of the enzyme catalytic loop with the DNA minor groove. Under the chosen conditions, the PWWP domain of Dnmt3a possessing lower affinity to DNA in comparison with the catalytic domain does not influence catalysis.",

keywords = "DNA damage, DNA methyltransferase, benzo[a]pyrene, intercalation, methylation, minor groove",

author = "Lukashevich, {O. V.} and Cherepanova, {N. A.} and A. Kolbanovsky and Geacintov, {N. E.} and Gromova, {E. S.}",

note = "Funding Information: ACKNOWLEDGEMENTS The authors thank Professor A. Jeltsch for the plas mid that carried the gene encoding hexahistidine derivative of methyltransferase Dnmt3a2. This work was supported by the Russian Founda tion for Basic Research, project no. 13 04 00727.",

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doi = "10.3103/S0027131414020059",

language = "English (US)",

volume = "69",

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AU - Lukashevich, O. V.

AU - Cherepanova, N. A.

AU - Kolbanovsky, A.

AU - Geacintov, N. E.

AU - Gromova, E. S.

N1 - Funding Information: ACKNOWLEDGEMENTS The authors thank Professor A. Jeltsch for the plas mid that carried the gene encoding hexahistidine derivative of methyltransferase Dnmt3a2. This work was supported by the Russian Founda tion for Basic Research, project no. 13 04 00727.

PY - 2014/3

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N2 - We have studied the impact of DNA damage by one of the most common carcinogens, benzo[a]pyrene, on the functioning of the truncated isoform of DNA methyltransferase Dnmt3a (Dnmt3a2). It is revealed with 30-mer model DNA substrates that DNA methylation rates are drastically reduced when the lesions disturb the structure of the Dnmt3a recognition site or hinder the interaction of the enzyme catalytic loop with the DNA minor groove. Under the chosen conditions, the PWWP domain of Dnmt3a possessing lower affinity to DNA in comparison with the catalytic domain does not influence catalysis.

AB - We have studied the impact of DNA damage by one of the most common carcinogens, benzo[a]pyrene, on the functioning of the truncated isoform of DNA methyltransferase Dnmt3a (Dnmt3a2). It is revealed with 30-mer model DNA substrates that DNA methylation rates are drastically reduced when the lesions disturb the structure of the Dnmt3a recognition site or hinder the interaction of the enzyme catalytic loop with the DNA minor groove. Under the chosen conditions, the PWWP domain of Dnmt3a possessing lower affinity to DNA in comparison with the catalytic domain does not influence catalysis.

KW - DNA damage

KW - DNA methyltransferase

KW - benzo[a]pyrene

KW - intercalation

KW - methylation

KW - minor groove

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Benzo[a]pyrene-derived DNA lesions decrease DNA methylation by murine methyltransferase DNMT3A2

Abstract

Keywords

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