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Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans.
Guilbaud, Axel; Ghanegolmohammadi, Farzan; Wang, Yijun; Leng, Jiapeng; Kreymerman, Alexander; Gamboa Varela, Jacqueline; Garbern, Jessica; Elwell, Hannah; Cao, Fang; Ricci-Blair, Elisabeth M; Liang, Cui; Balamkundu, Seetharamsing; Vidoudez, Charles; DeMott, Michael S; Bedi, Kenneth; Margulies, Kenneth B; Bennett, David A; Palmer, Abraham A; Barkley-Levenson, Amanda; Lee, Richard T; Dedon, Peter C.
Afiliación
  • Guilbaud A; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Ghanegolmohammadi F; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Wang Y; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Leng J; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Kreymerman A; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Gamboa Varela J; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Garbern J; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Elwell H; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Cao F; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Ricci-Blair EM; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Liang C; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Balamkundu S; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Vidoudez C; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • DeMott MS; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Bedi K; Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore.
  • Margulies KB; Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore.
  • Bennett DA; Harvard Center for Mass Spectrometry, Harvard University, Cambridge, MA 02138, USA.
  • Palmer AA; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Barkley-Levenson A; University of Pennsylvania Cardiovascular Institute, Philadelphia, PA, USA.
  • Lee RT; University of Pennsylvania Cardiovascular Institute, Philadelphia, PA, USA.
  • Dedon PC; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
Nucleic Acids Res ; 51(20): 10829-10845, 2023 11 10.
Article en En | MEDLINE | ID: mdl-37843128
DNA damage causes genomic instability underlying many diseases, with traditional analytical approaches providing minimal insight into the spectrum of DNA lesions in vivo. Here we used untargeted chromatography-coupled tandem mass spectrometry-based adductomics (LC-MS/MS) to begin to define the landscape of DNA modifications in rat and human tissues. A basis set of 114 putative DNA adducts was identified in heart, liver, brain, and kidney in 1-26-month-old rats and 111 in human heart and brain by 'stepped MRM' LC-MS/MS. Subsequent targeted analysis of these species revealed species-, tissue-, age- and sex-biases. Structural characterization of 10 selected adductomic signals as known DNA modifications validated the method and established confidence in the DNA origins of the signals. Along with strong tissue biases, we observed significant age-dependence for 36 adducts, including N2-CMdG, 5-HMdC and 8-Oxo-dG in rats and 1,N6-ϵdA in human heart, as well as sex biases for 67 adducts in rat tissues. These results demonstrate the potential of adductomics for discovering the true spectrum of disease-driving DNA adducts. Our dataset of 114 putative adducts serves as a resource for characterizing dozens of new forms of DNA damage, defining mechanisms of their formation and repair, and developing them as biomarkers of aging and disease.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ADN / Aductos de ADN Límite: Animals / Female / Humans / Male Idioma: En Revista: Nucleic Acids Res Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ADN / Aductos de ADN Límite: Animals / Female / Humans / Male Idioma: En Revista: Nucleic Acids Res Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos