TY - CHAP
T1 - O6-alkylguanine-DNA alkyltransferase
AU - Pegg, Anthony E.
AU - Kanugula, Sreenivas
AU - Loktionova, Natalia A.
PY - 2011
Y1 - 2011
N2 - Repair via O6-alkylguanine-DNA alkyltransferase (AGT) provides the major pathway for protection from agents that form small O6-alkylguanine lesions in DNA. This protein acts as a single agent to directly remove the alkyl group from DNA, restoring the integrity of DNA in one step. This review article describes the occurrence, structure, function, and mechanism of action of AGT proteins and some related proteins that link the repair of O6-alkylguanine lesions to nucleotide excision repair. The effects on susceptibility to carcinogens of transgenic alterations in AGT activity, the possible significance of human polymorphisms in AGT, and paradoxical effect of AGT proteins whereby they actually potentiate genetic damage caused by dihaloalkane and a number of other bifunctional electrophiles are also covered. Finally, the possible role of AGTs in providing resistance to cancer therapeutic alkylating agents and the development of AGT inhibitors that might overcome this resistance are outlined.
AB - Repair via O6-alkylguanine-DNA alkyltransferase (AGT) provides the major pathway for protection from agents that form small O6-alkylguanine lesions in DNA. This protein acts as a single agent to directly remove the alkyl group from DNA, restoring the integrity of DNA in one step. This review article describes the occurrence, structure, function, and mechanism of action of AGT proteins and some related proteins that link the repair of O6-alkylguanine lesions to nucleotide excision repair. The effects on susceptibility to carcinogens of transgenic alterations in AGT activity, the possible significance of human polymorphisms in AGT, and paradoxical effect of AGT proteins whereby they actually potentiate genetic damage caused by dihaloalkane and a number of other bifunctional electrophiles are also covered. Finally, the possible role of AGTs in providing resistance to cancer therapeutic alkylating agents and the development of AGT inhibitors that might overcome this resistance are outlined.
UR - http://www.scopus.com/inward/record.url?scp=84870707470&partnerID=8YFLogxK
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U2 - 10.1007/978-1-61737-995-6_15
DO - 10.1007/978-1-61737-995-6_15
M3 - Chapter
AN - SCOPUS:84870707470
SN - 9781617379949
T3 - Current Cancer Research
SP - 321
EP - 343
BT - Chemical Carcinogenesis
A2 - Penning, Trevor
ER -