title: Trypanosomal histone γH2A and the DNA damage response.
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.
authors.affiliation: London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Glover
authors.forename: David
authors.initials: D
authors.lastname: Horn
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D059447:Cell Cycle Checkpoints; D004249:DNA Damage; D004260:DNA Repair; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D015800:Protozoan Proteins; D051135:Rad51 Recombinase