{
  "abstract": "Eukaryotic genomic DNA is packaged into chromatin as nucleosomes, where it remains susceptible to reactive oxygen species (ROS) that generate the mutagenic lesion 8-oxo-7,8-dihydroguanine (8oxoG). While 8-oxoguanine DNA glycosylase 1 (OGG1) can initiate repair of 8oxoG base paired with C within the nucleosome core particle (NCP) in a position- dependent manner, it is unknown whether MutY homolog (MUTYH), the DNA glycosylase that excises misincorporated A opposite 8oxoG, can initiate repair of 8oxoG:A base pairs within NCPs. To address this, we combined cryo-EM, molecular dynamics (MD) simulations, and biochemical assays. We determined that MUTYH activity on nucleosomal 8oxoG:A is strongly suppressed, with detectable excision limited to the entry/exit region. Cryo-EM structures at four superhelical locations reveal that 8oxoG adopts the syn conformation and Hoogsteen base pairs with A, as in non-nucleosomal DNA, indicating that lesion presentation is not altered by the histone octamer. MD simulations further reveal that 8oxoG:A base pair dynamics and local DNA backbone perturbations are similar in nucleosomal and non-nucleosomal DNA. Together, these data establish that the NCP sterically excludes MUTYH from 8oxoG:A base pairs, making them largely inaccessible to MUTYH processing. This work ultimately provides mechanistic insight for the elevated G to T transversion rate observed in histone-bound DNA following oxidative stress.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Abigayle Vito"
    },
    {
      "name": "Justin Ling"
    },
    {
      "name": "Julia Ferrara"
    },
    {
      "name": "Caleb Jacques"
    },
    {
      "name": "Natacha Gillet"
    },
    {
      "name": "Roy González-Alemán"
    },
    {
      "name": "Yuya Qiu"
    },
    {
      "name": "Mohammad Hashemian"
    },
    {
      "name": "Carlos Trasviña-Arenas"
    },
    {
      "name": "Sheila David"
    },
    {
      "name": "Sarah Delaney"
    },
    {
      "name": "Emmanuelle Bignon"
    },
    {
      "name": "Bret Freudenthal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5kpjzzadva5em.bib",
  "cited_by": 1,
  "doi": "10.3390/biom16070999",
  "fulltext_url": null,
  "id": "5kpjzzadva5em",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://hal.science/hal-05756754v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.chim"
    ],
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7167838662",
  "pdf_url": "https://hal.science/hal-05756754/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-08",
  "publisher": "MDPI",
  "ris": "https://research.draconitic.com/paper/5kpjzzadva5em.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "hal-05756754",
      "source": "hal",
      "url": "https://hal.science/hal-05756754v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "8oxoG:A Is Structurally Accommodated in the Nucleosome Core Particle, Yet Inaccessible to MUTYH-Initiated DNA Repair",
  "title_text": "8oxoG:A Is Structurally Accommodated in the Nucleosome Core Particle, Yet Inaccessible to MUTYH-Initiated DNA Repair",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:58Z",
  "url": "https://research.draconitic.com/paper/5kpjzzadva5em",
  "venue": "Biomolecules",
  "versions": []
}