PMID: 8601571Jan 1, 1996Paper

DNA-repair methyltransferase as a molecular device for preventing mutation and cancer

Journal of Cancer Research and Clinical Oncology
M SekiguchiT Tuzuki

Abstract

Alkylation of DNA at the 0(6) position of guanine is regarded as one o f the most critical events leading to induction of mutations and cancers in organisms. Once 0(6)-methylguanine is formed, it can pair with thymine during DNA replication, the result being a conversion of the guanine.cytosine to an adenine.thymine pair in DNA, and such mutations are often found in tumors induced by alkylating agents. To counteract such effects, organisms possess a mechanism to repair 0(6)-methylguanine in DNA. An enzyme, 0(6)-methylguanine-DNA methyltransferase, is present in various organism, from bacteria to human cells, and appears to be responsible for preventing the occurrence of such mutations. The enzyme transfers methyl groups from 0(6)-methylguanine and other methylated moieties of the DNA to its own molecule, thereby repairing DNA lesions in a single-step reaction. To elucidate the role of methyltransferase in preventing cancers, animal models with altered levels of enzyme activity were generated. Transgenic mice carrying the foreign methyltransferase gene with functional promoters had higher levels of methyltransferase activity and showed a decreased susceptibility to N-nitroso compounds in regard to liver carcinogenesis. Mouse lin...Continue Reading

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Citations

Apr 18, 2000·Mutation Research·A E Pegg
Sep 19, 2003·DNA Repair·Yasumitsu TakagiMutsuo Sekiguchi
Apr 12, 2000·European Journal of Biochemistry·G Frosina
Jan 22, 2008·Antioxidants & Redox Signaling·Fabio AltieriSilvia Chichiarelli
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·H KawateM Sekiguchi
Mar 31, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Marco J ZeilmakerWout Slob
Jul 15, 1998·Critical Reviews in Clinical Laboratory Sciences·H R GriffithsJ Lunec
Dec 31, 2002·The Japanese Journal of Human Genetics·M Sekiguchi, K Sakumi
Dec 18, 2001·Environmental and Molecular Mutagenesis·S Kanugula, A E Pegg
Jan 6, 2018·Biomedicines·Ilya O VelegzhaninovOlesya M Vakhrusheva
Aug 2, 2002·The Journal of Biological Chemistry·Liping LiuF Peter Guengerich
Jun 12, 2008·The Journal of Toxicological Sciences·Masayoshi TakabatakeKunitoshi Mitsumori
Mar 30, 2000·Pharmacogenetics·R InoueT Suzuki
Dec 24, 2002·The Journal of Biological Chemistry·Joseph J RasimasMichael G Fried
Nov 17, 2006·Cancer Research·Stefano LandiPaul Brennan
Feb 12, 2020·The Journal of Physical Chemistry. B·Keisho Umesaki, Kei Odai
Jul 3, 2002·Biochemistry·Kieu X LuuRobert C Moschel
Sep 17, 2003·Biochemistry·F Peter GuengerichAnthony E Pegg
Nov 18, 2003·Chemical Research in Toxicology·Aviva S MeyerThomas E Spratt
Jan 29, 2003·Biochemistry·Joseph J RasimasAnthony E Pegg
Nov 16, 2005·Biochemistry·Qingming FangAnthony E Pegg

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