A Prokaryotic (6‐4) Photolyase with a DMRL Chromophore and an Iron–Sulfur Cluster

Abstract

Abstract Photolyases are flavoproteins that repair UV ‐damaged DNA using the energy of sunlight. The flavin adenine dinucleotide ( FAD ) chromophores of photolyases and the related cryptochromes are bound to the chromophore pocket in a U‐shaped conformation. Often, a second cofactor serves as antenna chromophore in photolyases. This can be methenyltetrahydrofolate ( MTHF ), 8‐hydroxy‐7,8‐didemethyl‐5‐deazariboflavin (8‐ HDF ), FAD, or flavin mononucleotide ( FMN ). Two kinds of DNA lesions are produced by UV light, cyclobutan‐pyrimidine dimers ( CPDs ) or (6‐4) photoproducts. These lesions are repaired by two different types of photolyases, namely the CPDs and (6‐4) photolyases. Recently, a new phylogenetic group of the photolyase cryptochrome family termed iron–sulfur bacterial cryptochromes/photolyases (FeS‐BCP) was discovered. Two members of this group, CryB from Rhodobacter sphaeroides and ‘photolyase related protein’ (PhrB) from Agrobacterium tumefaciens , carry a new antenna chromophore, 6,7‐dimethyl 8‐ ribityl‐lumazin ( DMRL ), and incorporate an 4Fe‐4S cluster. PhrB acts as a (6‐4) photolyase with a repair activity that is higher for double‐stranded than for single‐stranded DNA . There are presently more than 900 prokaryotic PhrB homologs in the database in which the characteristic cysteine residues for incorporation of the Fe‐S cluster and other key amino acids are conserved. This new group of (6‐4) photolyases with an Fe‐S cluster is thus widely distributed among prokaryotes. Unlike in other photolyases, the loop connecting the N‐terminal and the C‐terminal domains of PhrB interacts with the DNA lesion. A C‐terminal extension, which could have a regulatory function, interacts with the DNA . The comparison between PhrB and eukaryotic (6‐4) photolyases highlights a conserved His residue which is located next to the DNA lesion. This residue serves probably as proton donor/acceptor during the repair cycle.