Science China Life Sciences

, Volume 60, Issue 10, pp 1065–1076 | Cite as

Formation and repair of DNA-protein crosslink damage

  • Naeh L. Klages-Mundt
  • Lei LiEmail author


DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks (DPCs)—the covalent linkage of proteins with a DNA strand—are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents. Endogenously, DPCs are commonly derived through reactions with aldehydes, as well as through trapping of various enzymatic intermediates onto the DNA. Proteolytic cleavage of the protein moiety of a DPC is a general strategy for removing the lesion. This can be accomplished through a DPC-specific protease and and/or proteasome-mediated degradation. Nucleotide excision repair and homologous recombination are each involved in repairing DPCs, with their respective roles likely dependent on the nature and size of the adduct. The Fanconi anemia pathway may also have a role in processing DPC repair intermediates. In this review, we discuss how these lesions are formed, strategies and mechanisms for their removal, and diseases associated with defective DPC repair.


DNA-protein crosslinks nucleotide excision repair SPRTN Fanconi anemia 


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We thank Erica Lynn for helpful comments on the manuscript. This work was supported by the National Institutes of Health (CA179441, CA193124-Project 3 to Lei Li) and the Olive Stringer Endowed Professorship (Lei Li).


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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Experimental Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Program in Genetics and EpigeneticsThe University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesHoustonUSA

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