ArticleNucleic acids research2022
Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Selective targeting of human TREX1 exonuclease by small molecule inhibitors is mediated by a conformational switch.NAR molecular medicine · 2026Article
- DNA-Protein Cross-Link Formation and Cellular Toxicity by Chimeric Bis-Electrophiles.The Journal of organic chemistry · 2026Article
- Dirty Ends: Formation, Repair, and Biological Relevance of Non-Canonical DNA Terminal Structures.Genes · 2025Review
- Examination of a Chimeric Bis-Electrophile for Selective DNA-Protein Cross-Linking and Mechlorethamine Reveals an Unknown Source of Nitrogen Mustard Cytotoxicity.Journal of the American Chemical Society · 2025Article
- ADP-ribosylation of NuMA promotes DNA single-strand break repair and transcription.Cell reports · 2025Article
- DNA-Protein Cross-Links Derived from Abasic DNA Lesions: Recent Progress and Future Directions.Chemical research in toxicology · 2025Review
- Human 8-Oxoguanine Glycosylase OGG1 Cleaves Abasic Sites and Covalently Conjugates to 3'-DNA Termini via Cysteine and Histidine Addition.Chembiochem : a European journal of chemical biology · 2025Article
- Light-Driven Installation of Aminooxyhomolysine on Histones and Its Application for Synthesizing Stable and Site-Specific 3'-DNA-Histone Cross-Links.Bioconjugate chemistry · 2024Article
- Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.Nature communications · 2024Article
- Quantification of Intracellular DNA-Protein Cross-Links with N7-Methyl-2'-Deoxyguanosine and Their Contribution to Cytotoxicity.Chemical research in toxicology · 2024Article
- Tyrosyl-DNA phosphodiesterase 2 (Tdp2) repairs DNA-protein crosslinks and protects against double strand breaksFrontiers in cell and developmental biology · 2024Article
- Unprecedented reactivity of polyamines with aldehydic DNA modifications: structural determinants of reactivity, characterization and enzymatic stability of adducts.Nucleic acids research · 2023Article
- Tyrosyl-DNA phosphodiesterase 1 (TDP1) and SPRTN protease repair histone 3 and topoisomerase 1 DNA-protein crosslinksOpen biology · 2023Article
- Key Amino Acid Residues of Mitochondrial Transcription Factor A Synergize with Abasic (AP) Site Dynamics To Facilitate AP-Lyase Reactions.ACS chemical biology · 2023Article
- PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates.Nucleic acids research · 2023Article
- DNA-protein cross-links between abasic DNA damage and mitochondrial transcription factor A (TFAM).Nucleic acids research · 2023Article
- Local Alteration of Ionic Strength in a Nucleosome Core Particle and Its Effect onBiochemistry · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histones and many other proteins react with abundant endogenous DNA lesions, apurinic/apyrimidinic (abasic, AP) sites and/or 3'-phospho-α,β-unsaturated aldehyde (3'-PUA), to form unstable but long-lived Schiff base DNA-protein cross-links at 3'-DNA termini (3'-PUA-protein DPCs). Poly (ADP-ribose) polymerase 1 (PARP1) cross-links to the AP site in a similar manner but the Schiff base is reduced by PARP1's intrinsic redox capacity, yielding a stable 3'-PUA-PARP1 DPC. Eradicating these DPCs is critical for maintaining the genome integrity because 3'-hydroxyl is required for DNA synthesis and ligation. But how they are repaired is not well understood. Herein, we chemically synthesized 3'-PUA-aminooxylysine-peptide adducts that closely resemble the proteolytic 3'-PUA-protein DPCs, and found that they can be repaired by human tyrosyl-DNA phosphodiesterase 1 (TDP1), AP endonuclease 1 (APE1) and three-prime repair exonuclease 1 (TREX1). We characterized these novel repair pathways by measuring the kinetic constants and determining the effect of cross-linked peptide length, flanking DNA structure, and the opposite nucleobase. We further found that these nucleases can directly repair 3'-PUA-histone DPCs, but not 3'-PUA-PARP1 DPCs unless proteolysis occurs initially. Collectively, we demonstrated that in vitro 3'-PUA-protein DPCs can be repaired by TDP1, APE1, and TREX1 following proteolysis, but the proteolysis is not absolutely required for smaller DPCs.
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