Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins

DNA can be damaged by various intracellular and environmental alkylating agents to produce alkylation base lesions. These base damages, if not repaired promptly, may cause genetic changes that lead to diseases such as cancer. Recently, it was discovered that some of the alkylation DNA base damage can be directly removed by a family of proteins called the AlkB proteins that utilize a mononuclear non-heme iron(II) and alpha-ketoglutarate as cofactor and cosubstrate. These proteins activate dioxygen and perform an unprecedented oxidative dealkylation of the alkyl adducts on DNA heteroatoms. This review summarizes the discovery of this activity and the recent research advances in studying this unique DNA repair pathway. The focus is placed on the chemical mechanism and function of these proteins. (c) 2006 Elsevier Inc. All rights reserved.