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

Autor:	McLaughlin E; Institut Pasteur, Université Paris Cité, Trypanosome Molecular Biology, Department of Parasites and Insect Vectors, Paris, France; Sorbonne Université, Collège doctoral, Paris, France., Zavala Martinez MG; Institut Pasteur, Université Paris Cité, Trypanosome Molecular Biology, Department of Parasites and Insect Vectors, Paris, France., Dujeancourt-Henry A; Institut Pasteur, Université Paris Cité, Trypanosome Molecular Biology, Department of Parasites and Insect Vectors, Paris, France., Chaze T; Institut Pasteur, Université Paris Cité, Proteomics Platform, Mass Spectrometry for Biology Unit, Centre National de la Recherche Scientifique, UAR 2024, Paris, France., Gianetto QG; Institut Pasteur, Université Paris Cité, Proteomics Platform, Mass Spectrometry for Biology Unit, Centre National de la Recherche Scientifique, UAR 2024, Paris, France; Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics HUB, Paris, France., Matondo M; Institut Pasteur, Université Paris Cité, Proteomics Platform, Mass Spectrometry for Biology Unit, Centre National de la Recherche Scientifique, UAR 2024, Paris, France., Urbaniak MD; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK., Glover L; Institut Pasteur, Université Paris Cité, Trypanosome Molecular Biology, Department of Parasites and Insect Vectors, Paris, France. Electronic address: lucy.glover@pasteur.fr.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Sep; Vol. 300 (9), pp. 107657. Date of Electronic Publication: 2024 Aug 14.
DOI:	10.1016/j.jbc.2024.107657
Abstrakt:	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.)
Databáze:	MEDLINE
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