Phosphorylation of the canonical histone H2A marks foci of damaged DNA in malaria parasite [article]

Manish Goyal, Adina Heinberg, Vera Mitesser, Sofiya Kandelis-Shalev, Brajesh Kumar Singh, Ron Dzikowski
2020 bioRxiv   pre-print
Plasmodium falciparum parasites proliferate within circulating red blood cells and are responsible for the deadliest form of human malaria. These parasites are exposed to numerous intrinsic and external sources that could cause DNA damage, therefore, they have evolved efficient mechanisms to protect their genome integrity and allow them to proliferate in such conditions. In higher eukaryotes, double strand breaks rapidly lead to phosphorylation of the core histone variant H2A.X which marks the
more » ... ite of damaged DNA. We show that in P. falciparum that lacks the H2A.X variant, the canonical PfH2A is phosphorylated on serine 121 upon exposure to sources of DNA damage in a dose dependent manner. We further demonstrate that phosphorylated PfH2A is recruited to foci of damaged chromatin shortly after exposure to sources of damage, while the non-phosphorylated PfH2A remains spread throughout the nucleoplasm. In addition, we found that PfH2A phosphorylation is dynamic and as the parasite repairs its DNA over time, this phosphorylation is removed. We also demonstrate that these phosphorylation dynamics could be used to establish a novel and direct DNA repair assay in P. falciparum.
doi:10.1101/2020.11.06.372391 fatcat:el5lvhwpsnecxoiafpbiq3guy4