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Control of PML body dynamics and composition by PML protein SUMOylationwith an inducible phosphorylation system

Promyelocytic Leukemia Nuclear Bodies (PML-NBs) are a biomolecular condensate found in mammalian nuclei. They are implicated in a variety of cellular functions including anti-viral responses, DNA damage repair, and apoptosis. The PML protein is the single known scaffolding element of PML-NBs, and interactions between PML protein domains drive assembly of PML-NBs. I have identified a cell-cycle dependent switch in both the material properties and composition of PML-NBs. In interphase, PML-NBs behave like liquid droplets and contain multiple client proteins, features typical of other known condensates. However, as cells enter mitosis, PML-NBs become solid aggregates and dispel their client proteins. The goal of my research is to uncover the molecular mechanisms underlying this switch. My current hypothesis is that a reversible post-translational modification, SUMOylation, on the PML protein scaffold controls the material properties and composition of PML-NBs.

Image of GFP-PML in HeLa nuclei (red = SiR-tubulin)
Image of GFP-PML in HeLa nuclei (red = SiR-tubulin)