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.