O6-alkylguanine-DNA alkyltransferase

Anthony Pegg, Sreenivas Kanugula, Natalia A. Loktionova

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Title of host publicationChemical Carcinogenesis
EditorsTrevor Penning
Pages321-343
Number of pages23
DOIs
StatePublished - Dec 1 2011

Publication series

NameCurrent Cancer Research
Volume6
ISSN (Print)0940-0745

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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