The dominant DNA photo-damage product in UV irradiated bacterial endospores is a special thymine dimer, 5-thyminyl-5,6-dihydrothymine, which is commonly called the spore photoproduct or SP. SP is repaired rapidly by a metalloenzyme named the spore photoproduct lyase (SPL) when bacteria start germinating, thus posing little threat to their survival. Our group has proved that SPL utilizes an unprecedented radical transfer pathway involving at least one cysteine and two tyrosine residues for catalysis, which is composed of at least four hydrogen atom transfer (HAT) steps. This is the first protein-harbored radical transfer pathway found in the radical SAM superfamily (> 56,000 members); elucidating the key HAT processes in SPL catalysis is of significance to our understanding of the radical relay process in nature.Here, we focus on the mechanistic understanding of the first HAT step, the H-atom abstraction by the 5'-deoxyadenosyl radical. Current opinion in the field implies that it is a general H-atom abstraction process. However, our data indicate that this step requires a C-H bond activation, which is achieved via formation of an unprecedented Schiff base intermediate. A similar immediate may also be employed by other DNA damage repair enzymes such as the base excision repair enzymes. Schiff base formation may represent a unique property of some DNA damages which is utilized by nature to facilitate damage repair processes, but remain largely unnoticed by our scientific society.

C-H bond activation by a Schiff base intermediate in spore photoproduct lyase

248th National Meeting (2014)

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