I believe that this article is highly cited for two primary reasons. First, AlkB had long been known to be involved in a DNA repair process, but its role was unknown. This work finally revealed the answer to the mystery. Second, I believe these studies overturned a paradigm in the field, i.e., most researchers had thought that oxygen-related chemistry was limited to damaging reactions toward DNA, whereas our finding demonstrated that an oxidative mechanism was utilized for DNA repair.

The new discovery reported in Nature was the culmination of an extensive set of prior in vivo studies on AlkB carried out by Barbara Sedgwick and her coworkers at the Cancer Research UK, London Research Institute (LRI), along with intense investigations of various Fe(II)/alpha-ketoglutarate hydroxylases by my laboratory, and the added spark of a computational study done by L. Aravind and Eugene V. Koonin, of the National Center for Biotechnology Information at NIH, suggesting a connection between these diverse areas.

Our study defined the novel enzymatic mechanism by which AlkB is able to repair DNA damaged by selected reagents (which attach groups containing one or more carbon atoms) that interrupt normal DNA functions. Specifically, the enzyme "burns off" the damage by using oxidative chemistry.

I became involved in this research as part of my general interest in characterizing the diversity of reactions carried out by this class of enzyme.

We will continue to explore the substrate diversity of these enzymes, including an analysis of the roles of human homologues of AlkB that do not catalyze the oxidative demethylation chemistry.