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.