A dynamic connection between centromeres and ND10 proteins

ND10, otherwise known as nuclear dots, PML nuclear bodies or PODs, are punc tate foci in interphase nuclei that contain several cellular proteins. The functions of ND10 have not been well defined, but they are sensitive to ext ernal stimuli such as stress and virus infection, and they are disrupted in malignant promyelocytic leukaemia cells, Herpes simplex virus type 1 regul atory protein Vmw110 induces the proteasome-dependent degradation of ND10 c omponent proteins PML and Sp100, particularly the species of these proteins which are covalently conjugated to the ubiquitin-like protein SUMO-1. We h ave recently reported that Vmw110 also induces the degradation of centromer e protein CENP-C with consequent disruption of centromere structure, These observations led us to examine whether there were hitherto undetected conne ctions between ND10 and centromeres. In this paper we report that hDaxx and HP1 (which have been shown to interact with CENP-C and Sp100, respectively ) are present in a proportion of both ND10 and interphase centromeres, Furt hermore, the proteasome inhibitor MG132 induced an association between cent romeres and ND10 proteins PML and Sp100 in a significant number of cells in the G(2) phase of the cell cycle, These results imply that there is a dyna mic, cell cycle regulated connection between centromeres and ND10 proteins which can be stabilised by inhibition of proteasome-mediated proteolysis.