The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferaseCitation formats

  • External authors:
  • Pattama Senthong
  • Christopher L. Millington
  • Oliver J. Wilkinson
  • Andrew S. Marriott
  • Amanda J. Watson
  • Onrapak Reamtong
  • Claire E. Eyers
  • David M. Williams
  • Geoffrey P. Margison

Standard

The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase. / Senthong, Pattama; Millington, Christopher L.; Wilkinson, Oliver J.; Marriott, Andrew S.; Watson, Amanda J.; Reamtong, Onrapak; Eyers, Claire E.; Williams, David M.; Margison, Geoffrey P.; Povey, Andrew C.

In: Nucleic acids research., Vol. 41, No. 5, 03.2013, p. 3047-3055.

Research output: Contribution to journalArticle

Harvard

Senthong, P, Millington, CL, Wilkinson, OJ, Marriott, AS, Watson, AJ, Reamtong, O, Eyers, CE, Williams, DM, Margison, GP & Povey, AC 2013, 'The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase' Nucleic acids research., vol. 41, no. 5, pp. 3047-3055. https://doi.org/10.1093/nar/gks1476

APA

Senthong, P., Millington, C. L., Wilkinson, O. J., Marriott, A. S., Watson, A. J., Reamtong, O., ... Povey, A. C. (2013). The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase. Nucleic acids research., 41(5), 3047-3055. https://doi.org/10.1093/nar/gks1476

Vancouver

Senthong P, Millington CL, Wilkinson OJ, Marriott AS, Watson AJ, Reamtong O et al. The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase. Nucleic acids research. 2013 Mar;41(5):3047-3055. https://doi.org/10.1093/nar/gks1476

Author

Senthong, Pattama ; Millington, Christopher L. ; Wilkinson, Oliver J. ; Marriott, Andrew S. ; Watson, Amanda J. ; Reamtong, Onrapak ; Eyers, Claire E. ; Williams, David M. ; Margison, Geoffrey P. ; Povey, Andrew C. / The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase. In: Nucleic acids research. 2013 ; Vol. 41, No. 5. pp. 3047-3055.

Bibtex

@article{83b3d7855e364648974613abf4ffb1f7,
title = "The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase",
abstract = "The consumption of red meat is a risk factor in human colorectal cancer (CRC). One hypothesis is that red meat facilitates the nitrosation of bile acid conjugates and amino acids, which rapidly convert to DNA-damaging carcinogens. Indeed, the toxic and mutagenic DNA adduct O6-carboxymethylguanine (O6-CMG) is frequently present in human DNA, increases in abundance in people with high levels of dietary red meat and may therefore be a causative factor in CRC. Previous reports suggested that O6-CMG is not a substrate for the human version of the DNA damage reversal protein O 6-methylguanine-DNA methyltransferase (MGMT), which protects against the genotoxic effects of other O6-alkylguanine lesions by removing alkyl groups from the O6-position. We now show that synthetic oligodeoxyribonucleotides containing the known MGMT substrate O 6-methylguanine (O6-MeG) or O6-CMG effectively inactivate MGMT in vitro (IC50 0.93 and 1.8 nM, respectively). Inactivation involves the removal of the O6-alkyl group and its transfer to the active-site cysteine residue of MGMT. O6-CMG is therefore an MGMT substrate, and hence MGMT is likely to be a protective factor in CRC under conditions where O6-CMG is a potential causative agent. {\circledC} The Author(s) 2013.",
author = "Pattama Senthong and Millington, {Christopher L.} and Wilkinson, {Oliver J.} and Marriott, {Andrew S.} and Watson, {Amanda J.} and Onrapak Reamtong and Eyers, {Claire E.} and Williams, {David M.} and Margison, {Geoffrey P.} and Povey, {Andrew C.}",
year = "2013",
month = "3",
doi = "10.1093/nar/gks1476",
language = "English",
volume = "41",
pages = "3047--3055",
journal = "Nucleic Acids Res",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase

AU - Senthong, Pattama

AU - Millington, Christopher L.

AU - Wilkinson, Oliver J.

AU - Marriott, Andrew S.

AU - Watson, Amanda J.

AU - Reamtong, Onrapak

AU - Eyers, Claire E.

AU - Williams, David M.

AU - Margison, Geoffrey P.

AU - Povey, Andrew C.

PY - 2013/3

Y1 - 2013/3

N2 - The consumption of red meat is a risk factor in human colorectal cancer (CRC). One hypothesis is that red meat facilitates the nitrosation of bile acid conjugates and amino acids, which rapidly convert to DNA-damaging carcinogens. Indeed, the toxic and mutagenic DNA adduct O6-carboxymethylguanine (O6-CMG) is frequently present in human DNA, increases in abundance in people with high levels of dietary red meat and may therefore be a causative factor in CRC. Previous reports suggested that O6-CMG is not a substrate for the human version of the DNA damage reversal protein O 6-methylguanine-DNA methyltransferase (MGMT), which protects against the genotoxic effects of other O6-alkylguanine lesions by removing alkyl groups from the O6-position. We now show that synthetic oligodeoxyribonucleotides containing the known MGMT substrate O 6-methylguanine (O6-MeG) or O6-CMG effectively inactivate MGMT in vitro (IC50 0.93 and 1.8 nM, respectively). Inactivation involves the removal of the O6-alkyl group and its transfer to the active-site cysteine residue of MGMT. O6-CMG is therefore an MGMT substrate, and hence MGMT is likely to be a protective factor in CRC under conditions where O6-CMG is a potential causative agent. © The Author(s) 2013.

AB - The consumption of red meat is a risk factor in human colorectal cancer (CRC). One hypothesis is that red meat facilitates the nitrosation of bile acid conjugates and amino acids, which rapidly convert to DNA-damaging carcinogens. Indeed, the toxic and mutagenic DNA adduct O6-carboxymethylguanine (O6-CMG) is frequently present in human DNA, increases in abundance in people with high levels of dietary red meat and may therefore be a causative factor in CRC. Previous reports suggested that O6-CMG is not a substrate for the human version of the DNA damage reversal protein O 6-methylguanine-DNA methyltransferase (MGMT), which protects against the genotoxic effects of other O6-alkylguanine lesions by removing alkyl groups from the O6-position. We now show that synthetic oligodeoxyribonucleotides containing the known MGMT substrate O 6-methylguanine (O6-MeG) or O6-CMG effectively inactivate MGMT in vitro (IC50 0.93 and 1.8 nM, respectively). Inactivation involves the removal of the O6-alkyl group and its transfer to the active-site cysteine residue of MGMT. O6-CMG is therefore an MGMT substrate, and hence MGMT is likely to be a protective factor in CRC under conditions where O6-CMG is a potential causative agent. © The Author(s) 2013.

U2 - 10.1093/nar/gks1476

DO - 10.1093/nar/gks1476

M3 - Article

VL - 41

SP - 3047

EP - 3055

JO - Nucleic Acids Res

JF - Nucleic Acids Res

SN - 0305-1048

IS - 5

ER -