BreviaAurora Kinase B Phosphorylates Histone H3.3 at Serine 31 during Mitosis in Mammalian Cells

- High content imaging-based kinome siRNA and inhibitor screens were performed.
- Aurora kinase B was the top hit for H3.3S31 phosphorylation in both screens.
- Aurora kinase B phosphorylates nucleosomal H3.3 at S31 in vitro.

Serine 31 of histone H3.3 is phosphorylated during mitosis in mammalian cells and has been shown to influence chromosome segregation. We established a screening system to identify candidate kinase(s) phosphorylating H3.3S31 by using siRNA library targeting 720 human kinases, and we confirmed the results with an independent kinase inhibitor screen. Aurora kinase B was the best candidate hit in both screens. Moreover, the kinase activity of Aurora B on H3.3S31 was biochemically confirmed with nucleosomal substrates in vitro.

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