Engineering of a O6-alkylguanine-DNA alkyltransferase chimera and repair of O4-alkyl thymidine adducts and O6-alkylene-2′-deoxyguanosine cross-linked DNA

Abstract

A soluble human O⁶-alkylguanine-DNA alkyltransferase (hAGT) chimera was engineered containing the active site of OGT (residues 139–159) and an additional S134P mutation. The resulting hAGT chimera not only retained hAGT's ability to repair bulky O⁶-alkylene-2′-deoxyguanosine interstrand cross-linked DNA damage but also displayed enhanced repair of various O⁴-alkyl thymidine adducts.