DNA–protein crosslinks (DPCs) are highly toxic DNA adducts, but whether dedicated DPC-repair mechanisms exist was until recently unknown. This has changed with discoveries made in yeast and Xenopus laevis that revealed a protease-based DNA-repair pathway specific for DPCs. Importantly, mutations in the gene encoding the putative human homologue of a yeast DPC protease cause a human premature ageing and cancer predisposition syndrome. Thus, DPC repair is a previously overlooked genome-maintenance mechanism that may be essential for tumour suppression.
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S.J. is supported by the Max Planck Society, Deutsche Forschungsgemeinschaft, Center for Integrated Protein Science Munich, RUBICON EU Network of Excellence, a European Research Council Advanced Grant and the Louis-Jeantet Foundation.
The authors declare no competing financial interests.
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Stingele, J., Jentsch, S. DNA–protein crosslink repair. Nat Rev Mol Cell Biol 16, 455–460 (2015). https://doi.org/10.1038/nrm4015
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