{
  "abstract": "To identify the genes and pathways required for the survival of MYC-amplified cancers, we engineered an isogenic cell system in which transformation is driven by oncogenic MYC. Using a genome-scale CRISPR-Cas9 library, we identified the mitochondrial membrane translocase TIMM17A as uniquely essential for the survival of MYC-transformed cells. This dependency arises from MYC-driven suppression of TIMM17B, the paralog of TIMM17A. TIMM17A/B is an essential component of the TIM23 mitochondrial protein import complex, and the MYC-induced suppression of TIMM17B creates a strong dependency on TIMM17A. N-acetylaspartate supplementation rescued TIMM17A dependency in MYC-amplified cell lines, highlighting the unique and crucial role of this metabolite in the cell fitness of MYC-amplified cancers. These observations identify a paralog dependency required for the survival of a subset of MYC-driven cancers.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.",
    "Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.",
    "Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02115, USA.",
    "Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sydney M. Moyer",
      "orcid": "0000-0002-2911-4058"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nina Ilic",
      "orcid": "0009-0001-3749-4601"
    },
    {
      "affs": [
        0
      ],
      "name": "Sydney Gang"
    },
    {
      "affs": [
        1
      ],
      "name": "Lucas Dailey",
      "orcid": "0000-0003-3204-9565"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Sehyun Oh",
      "orcid": "0009-0003-0366-2413"
    },
    {
      "affs": [
        0
      ],
      "name": "Jasmine Stavridi"
    },
    {
      "affs": [
        0
      ],
      "name": "Gaia Taig",
      "orcid": "0009-0003-5269-8551"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kathia E. Rodarte",
      "orcid": "0000-0001-7608-7585"
    },
    {
      "affs": [
        0
      ],
      "name": "Joseph D. DeAngelo",
      "orcid": "0000-0001-5008-0414"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrea Jiang",
      "orcid": "0009-0003-0772-7093"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Brian H. Shim"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jonathan P. Rennhack",
      "orcid": "0000-0001-6306-195X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "John R. Jacob",
      "orcid": "0000-0003-4447-6660"
    },
    {
      "affs": [
        0
      ],
      "name": "Melis A. Akinci",
      "orcid": "0000-0003-0104-9095"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jonathan So",
      "orcid": "0000-0001-9919-2476"
    },
    {
      "affs": [
        0
      ],
      "name": "Helen Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Federica Piccioni",
      "orcid": "0000-0003-1210-3210"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jessica A. Talamas",
      "orcid": "0000-0002-7887-6294"
    },
    {
      "affs": [
        3
      ],
      "name": "Hans R. Widlund",
      "orcid": "0000-0002-7506-2447"
    },
    {
      "affs": [
        1
      ],
      "name": "David E. Root",
      "orcid": "0000-0001-5122-861X"
    },
    {
      "affs": [
        1
      ],
      "name": "Clary B. Clish",
      "orcid": "0000-0001-8259-9245"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Nika N. Danial",
      "orcid": "0000-0003-4842-1827"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "William C. Hahn",
      "orcid": "0000-0003-2840-9791"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/39rwjf1wx5hwk.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aej2662",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13742171/",
  "id": "39rwjf1wx5hwk",
  "issns": [
    "2375-2548"
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  "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.aej2662",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biomedicine and Life Sciences"
    ],
    [
      "heading",
      "Cancer"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "SciAdv r-articles"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": "PMC13742171",
  "pmid": "42993843",
  "published": "2026-11-06",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/39rwjf1wx5hwk.ris",
  "sources": [
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      "first_seen": "2026-11-07T00:20:49Z",
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      "url": "https://www.science.org/doi/abs/10.1126/sciadv.aej2662"
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    {
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  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Cell Biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "heading:Cancer",
      "subfield": "oncology"
    }
  ],
  "title": "MYC primes a paralog synthetic lethality involving the mitochondrial translocase subunits TIMM17A and TIMM17B and N-Acetylaspartate",
  "title_text": "MYC primes a paralog synthetic lethality involving the mitochondrial translocase subunits TIMM17A and TIMM17B and N-Acetylaspartate",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:23:03Z",
  "url": "https://research.draconitic.com/paper/39rwjf1wx5hwk",
  "venue": "Science Advances",
  "versions": []
}