ArticlebioRxiv : the preprint server for biology2025
The DREAM complex links somatic mutation, lifespan, and disease.
Zane Koch, Shuvro P Nandi, Kate Licon, Arturo Bujarrabal-Dueso, David H Meyer, Safa Saeed, Pirunthan Perampalam, Frederick A Dick, Björn Schumacher, Ludmil B Alexandrov and 1 more
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In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
11 authors.
Zane KochProgram in Bioinformatics and Systems Biology, University of California San Diego, La Jolla CA, 92093, USA.ORCID 0000-0003-2259-3065 Shuvro P NandiDepartment of Bioengineering, University of California San Diego, La Jolla, California, USA.ORCID 0000-0003-4855-4697 Kate LiconDepartment of Medicine, University of California San Diego, La Jolla California, 92093, USA.
Arturo Bujarrabal-DuesoInstitute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne, Cologne, Germany.ORCID 0000-0003-3053-8293 David H MeyerInstitute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne, Cologne, Germany.
Safa SaeedDepartment of Bioengineering, University of California San Diego, La Jolla, California, USA.
Pirunthan PerampalamDepartment of Pathology and Laboratory Medicine, Verspeeten Family Cancer Centre, Children's Health Research Institute, Western University, London, N6A 4L6, Ontario, Canada.
Frederick A DickDepartment of Pathology and Laboratory Medicine, Verspeeten Family Cancer Centre, Children's Health Research Institute, Western University, London, N6A 4L6, Ontario, Canada.
Björn SchumacherInstitute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne, Cologne, Germany.ORCID 0000-0001-6097-5238 Ludmil B AlexandrovProgram in Bioinformatics and Systems Biology, University of California San Diego, La Jolla CA, 92093, USA.ORCID 0000-0003-3596-4515 Trey IdekerProgram in Bioinformatics and Systems Biology, University of California San Diego, La Jolla CA, 92093, USA.ORCID 0000-0002-1708-8454 Funding
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3MThe Cancer Cell Map Initiative v2.0U54CA274502 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trey Ideker · 2022 to 2026
$14.2MDetecting Mutational Signatures of Environmental Mutagens in Heathy Individuals for Personalized Cancer PreventionR01ES032547 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALEXANDROV, LUDMIL B · 2021 to 2025
$3.4MIllumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600kNCI NIH HHS U54 CA274502NIEHS NIH HHS R01 ES032547NIGMS NIH HHS P41 GM103504NIH HHS S10 OD026929
6 · The paper itselfAbstract
The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM activity and somatic mutations across a single-cell atlas of 21 mouse tissues shows that cellular niches with lower DREAM activity have decreased mutation rates. Second, DREAM activity predicts the varied lifespans observed across 92 mammals, with low activity marking longer-lived species. Third, reduced DREAM activity in Alzheimer's patients predicts late disease onset and decreased risk for severe neuropathology. Finally, we show DREAM knockout protects against mutation accumulation
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PMID41000880
PMCPMC12458141
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