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DNA–protein crosslink repair

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Abstract

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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Figure 1: The formation of DPCs.
Figure 2: Consequences and characteristics of DPCs.
Figure 3: Modes of DPC repair and tolerance.

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Acknowledgements

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.

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  1. Julian Stingele

    Present address: Julian Stingele was previously at the Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. Present address: The Francis Crick Institute, Clare Hall Laboratory, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.,

Authors and Affiliations

  1. Stefan Jentsch is at the Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.,

    Julian Stingele & Stefan Jentsch

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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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