Structural insights into a class II photolyase: A new theme of light-driven DNA repair

The major UV-induced lesion in duplex DNA is the cis-syn isomer of the cyclobutane pyrimidine dimer (CPD) which is repaired by substrate-specific DNA photolyases using blue/near-UV light. Since discovery of this catalytic mechanism called photoreactivation, several microbial class I photolyases have been functionally and structurally characterized. In contrast, the state of research on class II photolyases which form a distinct phylogenetic branch and are mostly restricted to higher, multicellular eukaryotes is in the beginning.

Here we report the functional and structural characterization of the class II photolyase from the methanogenic archaeon Methanosarcina mazei (MmCPDII) which has a remarkable close relationship to plant and other metazoan enzymes. MmCPDII catalyzes light-driven DNA repair as well as photoreduction. Our crystal structures of this class II photolyase alone and as a complex with duplex DNA comprising a synthetic CPD lesion reveal new insights into this unexplored field of DNA repair.