Pathways
Repair of O6-MeG by MGMT
Description:
Alkylating agents are compounds that cause cytotoxic DNA damage as well as collateral mutagenic damage. They work by adding an alkyl group to the guanine base of the DNA molecule and cause breakage of DNA strands. Methylation at the guanine O6 position forms the greatest promutagenic and lethal toxic DNA lesion. O(6)-methylguanine (O6-meG) is formed in DNA by alkylation of the oxygen atom of guanine, most often by N-nitroso compounds (NOC) and sometimes due to methylation by other compounds such as endogenous S-adenosyl...
References:
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DNA damage induced by alkylating agents and repair pathways.
J Nucleic Acids. 2010 Nov 21;2010:543531. doi: 10.4061/2010/543531. -
Balancing repair and tolerance of DNA damage caused by alkylating agents.
Nat Rev Cancer. 2012 Jan 12;12(2):104-20. doi: 10.1038/nrc3185. -
O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas.
Cell Death Dis. 2013 Oct 24;4(10):e876. doi: 10.1038/cddis.2013.388. -
Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities.
Trends Biochem Sci. 2017 Mar;42(3):206-218. doi: 10.1016/j.tibs.2016.10.001. Epub 2016 Nov 2.
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