Formation and repair of DNA-protein crosslink damage

Science China. Life Sciences
Naeh L Klages-Mundt, Lei Li

Abstract

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 disease...Continue Reading

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Citations

Jan 27, 2020·Environmental and Molecular Mutagenesis·Julie Rageul, Hyungjin Kim
Sep 6, 2019·International Journal of Molecular Sciences·Janina EnderleHolger Puchta
Mar 23, 2019·Science China. Life Sciences·Chunchun WuMing Zhou
May 13, 2020·Neural Regeneration Research·Thais Ceresér VilelaRicardo Aurino de Pinho
Jan 8, 2021·Frontiers in Cell and Developmental Biology·Manideep C PachvaRegina Groisman
Jan 7, 2020·Molecular Cell·Nataliia SerbynFrançoise Stutz
Nov 16, 2019·Chemical Research in Toxicology·Mengdi ShangChuanzheng Zhou
Aug 31, 2021·The Journal of Biological Chemistry·Pratibha P Ghodke, F Peter Guengerich

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