Trypanosomal histone γH2A and the DNA damage response.

Molecular and Biochemical Parasitology
Lucy Glover, David Horn

Abstract

DNA damage and repair in trypanosomatids impacts virulence, drug resistance and antigenic variation but, currently, little is known about DNA damage responses or cell cycle checkpoints in these divergent protozoa. One of the earliest markers of DNA damage in eukaryotes is γH2A(X), a serine phosphorylated histone H2A (variant). Here, we report the identification and initial characterization of γH2A in Trypanosoma brucei. We identified Thr(130) within the replication-dependent histone H2A as a candidate phosphorylation site and found that the abundance of this trypanosomal γH2A increased in vivo in response to DNA damage. Nuclear γH2A foci mark the sites of putative natural replication fork stalling, sites of meganuclease-induced DNA double strand breaks and sites of methyl methanesulphonate-induced DNA damage. Naturally occurring and meganuclease-induced γH2A and RAD51 double-positive repair foci are typically found in S-phase or G(2) nuclei. The results link trypanosomal γH2A, with an unusual histone modification motif, to DNA damage sensing and mitotic checkpoint signaling.

References

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Citations

Jul 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Nicola BakerDavid Horn
Mar 7, 2014·Microbiology and Molecular Biology Reviews : MMBR·Marie-Michelle GenoisJean-Yves Masson
Nov 27, 2018·PLoS Neglected Tropical Diseases·James A ThomasDavid Horn
Aug 10, 2017·Molecular Microbiology·Emma Louise MeredithShane R Wilkinson
Oct 22, 2016·Molecular Microbiology·Maria ValenteDolores González-Pacanowska
May 30, 2020·PLoS Neglected Tropical Diseases·Rubens Daniel Miserani MagalhãesMaria Júlia Manso Alves
Jul 3, 2020·Genes·Arijit BhattacharyaChristopher Fernandez-Prada
Jun 19, 2018·Nucleic Acids Research·Juan-José VasquezT Nicolai Siegel
Sep 25, 2017·Frontiers in Microbiology·Andrew A KelsoMichael G Sehorn
Jan 23, 2013·Cellular Microbiology·Nilmar Silvio Moretti, Sergio Schenkman
Jan 9, 2021·Frontiers in Cell and Developmental Biology·Paula Andrea MarinMaria Carolina Elias
Sep 29, 2019·International Journal for Parasitology. Drugs and Drug Resistance·Camino Gutiérrez-CorboYolanda Pérez-Pertejo
Mar 11, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Vinicius Santana NunesSergio Schenkman
Nov 5, 2019·Journal of Molecular Biology·Arpita SahaBibo Li

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Methods Mentioned

BETA
dissection
transfection
enzyme-linked immunosorbent assay
fluorescence microscopy
light microscopy

Software Mentioned

Metamorph

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