ArticleProceedings of the National Academy of Sciences of the United States of America2003
Suppressed catalytic activity of base excision repair enzymes on rotationally positioned uracil in nucleosomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 160 citations in OpenAlex.
- CRISPR-mediated gap-based replacement enables site-specific DNA lesion insertion into long DNA and nucleosomes.Nucleic acids research · 2026Article
- Navigating the base excision repair pathway in chromatin-focus on oxidative DNA damage.Nucleic acids research · 2026Review
- 8oxoG:A Is Structurally Accommodated in the Nucleosome Core Particle, Yet Inaccessible to MUTYH-Initiated DNA Repair.Biomolecules · 2026Article
- Sequence context and methylation interact to shape germline mutation rate variation at CpG sites.PLoS genetics · 2026Article
- Sequence context and methylation interact to shape germline mutation rate variation at CpG sites.bioRxiv : the preprint server for biology · 2026Article
- Base excision repair in chromatin: A tug-of-war for DNA damage.DNA repair · 2025Review
- Mechanisms underlying low mutation rates in mammalian oocytes and preimplantation embryos.Nucleic acids research · 2025Review
- A Method for Constructing Nucleosome Arrays with Spatially Defined Histone PTMs and DNA Damage.Angewandte Chemie (International ed. in English) · 2025Article
- A Balancing Act: Thymine DNA Glycosylase Combines Sequence and Rotational Preferences To Define Lesion Excision in the Nucleosome Core Particle.Biochemistry · 2025Article
- Structural basis of gap-filling DNA synthesis in the nucleosome by DNA Polymerase β.Nature communications · 2025Article
- Article
- The chromatin remodeler ERCC6 and the histone chaperone NAP1 are involved in apurinic/apyrimidinic endonuclease-mediated DNA repair.The Plant cell · 2024Article
- Redox-Based Defect Detection in Packed DNA: Insights from Hybrid Quantum Mechanical/Molecular Mechanics Molecular Dynamics Simulations.Journal of chemical theory and computation · 2023Article
- UV-DDB as a General Sensor of DNA Damage in Chromatin: Multifaceted Approaches to Assess Its Direct Role in Base Excision Repair.International journal of molecular sciences · 2023Review
- UV-DDB stimulates the activity of SMUG1 during base excision repair of 5-hydroxymethyl-2'-deoxyuridine moieties.Nucleic acids research · 2023Article
- Ionic strength modulates excision of uracil by SMUG1 from nucleosome core particles.DNA repair · 2023Article
- Generation of Recombinant Nucleosomes Containing Site-Specific DNA Damage.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Cooperative interaction between AAG and UV-DDB in the removal of modified bases.Nucleic acids research · 2022Article
- Colorimetric Detection of DNase Type I 3'OH DNA Ends Using an Isothermal Amplification-Assisted Paper-Based Analytical Device.Biosensors · 2022Article
- Structural basis for APE1 processing DNA damage in the nucleosome.Nature communications · 2022Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The majority of DNA in eukaryotic cells exists in the highly condensed structural hierarchy of chromatin, which presents a challenge to DNA repair enzymes in that recognition, incision, and restoration of the original sequence at most sites must take place within these structural constraints. To test base excision repair (BER) activities on chromatin substrates, an in vitro system was developed that uses human uracil DNA glycosylase (UDG), apyrimidinic/apurinic endonuclease (APE), and DNA polymerase beta (pol beta) on homogeneously damaged, rotationally positioned DNA in nucleosomes. We find that UDG and APE carry out their combined catalytic activities with reduced efficiency on nucleosome substrates ( approximately 10% of that on naked DNA). Furthermore, these enzymes distinguish between two different rotational settings of the lesion on the histone surface, showing a 2- to 3-fold difference in activity between uracil facing "toward" and "away from" the histones. However, UDG and APE will digest such substrates to completion in a concentration-dependent manner. Conversely, the synthesis activity of pol beta is inhibited completely by nucleosome substrates and is independent of enzyme concentration. These results suggest that the first two steps of BER, UDG and APE, may occur "unassisted" in chromatin, whereas downstream factors in this pathway (i.e., pol beta) may require nucleosome remodeling for efficient DNA BER in at least some regions of chromatin in eukaryotic cells.
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