Abstract
The mammalian cell nucleus contains a variety of organelles or nuclear bodies which contribute to key nuclear functions. Promyelocytic leukemia nuclear bodies (PML NBs) are involved in the regulation of apoptosis, antiviral responses, the DNA damage response and chromatin structure, but their precise biochemical function in these nuclear pathways is unknown. One strategy to tackle this problem is to assess the biophysical properties of the component parts of these macromolecular assemblies in living cells. In this study we determined PML NB assembly dynamics by live cell imaging, combined with mathematical modeling. For the first time, dynamics of PML body formation were measured in cells lacking endogenous PML. We show that all six human nuclear PML isoforms are able to form nuclear bodies in PML negative cells. All isoforms exhibit individual exchange rates at NBs in PML positive cells but PML I, II, III and IV are static at nuclear bodies in PML negative cells, suggesting that these isoforms require additional protein partners for efficient exchange. PML V turns over at PML Nbs very slowly supporting the idea of a structural function for this isoform. We also demonstrate that SUMOylation of PML at Lysine positions K160 and/or K490 are required for nuclear body formation in vivo.We propose a model in which the isoform specific residence times of PML provide both, structural stability to function as a scaffold and flexibility to attract specific nuclear proteins for efficient biochemical reactions at the surface of nuclear bodies.MCS code: 92C37
Highlights
The cell nucleus is functionally devoted to the realization and protection of the genetic material it contains in the form of chromosome territories [1]
We demonstrate that SUMOylation of PML at Lysine positions K160 and/or K490 are required for nuclear body formation in vivo.We propose a model in which the isoform specific residence times of PML provide both, structural stability to function as a scaffold and flexibility to attract specific nuclear proteins for efficient biochemical reactions at the surface of nuclear bodies
The objective of the current study was to study the formation of Promyelocytic leukemia nuclear bodies (PML NBs) in the absence of endogenous PML expression
Summary
The cell nucleus is functionally devoted to the realization and protection of the genetic material it contains in the form of chromosome territories [1]. The mammalian cell nucleus contains a variety of internal structures, termed domains or bodies [5]. These macromolecular assemblies include nucleoli, speckles, Cajal bodies, and promyelocytic leukemia nuclear bodies (PML NBs) [6,7]. While the structure and function of nucleoli, which is mainly ribosomal RNA synthesis and ribosome biogenesis, is very well understood, the precise biochemical function of speckles, Cajal bodies or PML nuclear bodies is not known [6]. Again, of the nucleolus which builds on ribosomal RNA genes, it remains elusive if and how the other nuclear domains are spatially and functionally related to sites of transcritpion, replication, DNA repair, or how they relate to specific genomic regions [7]
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