Locating and severing lethal links in DNA
Chemical lesions in the genetic material DNA can have catastrophic consequences for cells, and even for the organism concerned. This explains why the efficient identification and rapid repair of DNA damage is vital for survival. DNA-protein crosslinks (DPCs), which are formed when proteins are adventitiously attached to DNA, are particularly harmful. DPCs are removed by the action of a dedicated enzyme—the protease SPRTN—which cleaves the bond between the protein and the DNA. Up to now, how SPRTN recognizes such crosslinks, which can differ significantly in structure, has remained unclear. Now a team led by Professor Julian Stingele (LMU Gene Center), in cooperation with Professor Michael Sattler (Helmholtz Zentrum München and Technical University of Munich), has shown that the enzyme utilizes a modular recognition mechanism to detect such sites, such that it is activated only under highly specific conditions. The new findings appear in the journal Molecular Cell.