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

被引:177
作者
Margison, GP [1 ]
Santibáñez-Koref, MF
机构
[1] Paterson Inst Canc Res, CRC Carcinogenesis Grp, Manchester M20 9BX, Lancs, England
[2] Max Delbruck Ctr Mol Med, Berlin, Germany
关键词
D O I
10.1002/bies.10063
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, O-6-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. BioEssays 24:255-266,2002. (C) 2002 Wiley Periodicals, Inc.;
引用
收藏
页码:255 / 266
页数:12
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