Phosphoproteomic analysis of the response to DNA damage in Trypanosoma brucei.

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  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Trypanosoma brucei brucei*/metabolism ; Trypanosoma brucei brucei*/genetics ; Phosphoproteins*/metabolism ; Phosphoproteins*/genetics ; Protozoan Proteins*/metabolism ; Protozoan Proteins*/genetics; Phosphorylation ; DNA Damage ; Proteomics/methods ; Proteome/metabolism ; DNA Breaks, Double-Stranded ; DNA Repair ; Histones/metabolism
    • Abstract:
      Damage to the genetic material of the cell poses a universal threat to all forms of life. The DNA damage response is a coordinated cellular response to a DNA break, key to which is the phosphorylation signaling cascade. Identifying which proteins are phosphorylated is therefore crucial to understanding the mechanisms that underlie it. We have used stable isotopic labeling of amino acids in cell culture-based quantitative phosphoproteomics to profile changes in phosphorylation site abundance following double stranded DNA breaks, at two distinct loci in the genome of the single cell eukaryote Trypanosoma brucei. Here, we report on the T. brucei phosphoproteome following a single double-strand break at either a chromosome internal or subtelomeric locus, specifically the bloodstream form expression site. We detected >6500 phosphorylation sites, of which 211 form a core set of double-strand break responsive phosphorylation sites. Along with phosphorylation of canonical DNA damage factors, we have identified two novel phosphorylation events on histone H2A and found that in response to a chromosome internal break, proteins are predominantly phosphorylated, while a greater proportion of proteins dephosphorylated following a DNA break at a subtelomeric bloodstream form expression site. Our data represent the first DNA damage phosphoproteome and provides novel insights into repair at distinct chromosomal contexts in T. brucei.
      Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
      (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: DNA break; DNA damage response; Trypanosoma brucei; phosphoproteomics
    • Accession Number:
      0 (Phosphoproteins)
      0 (Protozoan Proteins)
      0 (Proteome)
      0 (Histones)
    • Publication Date:
      Date Created: 20240811 Date Completed: 20241008 Latest Revision: 20241008
    • Publication Date:
      20250114
    • Accession Number:
      PMC11408851
    • Accession Number:
      10.1016/j.jbc.2024.107657
    • Accession Number:
      39128729