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O6-alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy

Item Type:Review
Title:O6-alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy
Creators Name:Margison, G.P. and Santibanez-Koref, M.F.
Abstract:The DNA in human cells is continuously undergoing damage as consequences of both endogenous processes and exposure to exogenous agents. The resulting structural changes can be repaired by a number of systems that function to preserve genome integrity. Most pathways are multicomponent, involving incision in the damaged DNA strand and resynthesis using the undamaged strand as a template. In contrast, O6-alkylguanine-DNA alkyltransferase is able to act as a single protein that reverses specific types of alkylation damage simply by removing the offending alkyl group, which becomes covalently attached to the protein and inactivates it. The types of damage that ATase repairs are potentially toxic, mutagenic, recombinogenic and clastogenic. They are generated by certain classes of carcinogenic and chemotherapeutic alkylating agents. There is consequently a great deal of interest in this repair system in relation to both carcinogenesis and cancer chemotherapy.
Keywords:Alkylating Agents, Carcinogens, DNA Repair, Neoplasms, Neoplastic Cell Transformation, O(6)-Methylguanine-DNA Methyltransferase, Animals
Publisher:Company Of Biologists Ltd
Page Range:255-266
Date:1 January 2002
Official Publication:https://doi.org/10.1002/bies.10063
PubMed:View item in PubMed

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