HA95 is a protein of the chromatin and nuclear matrix regulating nuclear envelope dynamics

We report a role for HA95, a nuclear protein with high homology to the nucl ear A-kinase anchoring protein AKAP95, in the regulation of nuclear envelop e-chromatin interactions. Biochemical and photobleaching data indicate that HA95 is tightly associated with chromatin and the nuclear matrix/lamina ne twork in interphase, and bound to chromatin at mitosis, HA95 resides in a c omplex together with lamin B receptor (LBR), lamina-associated polypeptide (LAP)2 and emerin, integral proteins of the inner nuclear membrane. Cross-l inking experiments, however, illustrate a tight association of HA95 with LB R and LAP2 only. Intra-nuclear blocking of HA95 with anti HA95 antibodies a bolishes nuclear breakdown in a mitotic HeLa cell extract, The antibodies i nhibit nuclear membrane breakdown and chromatin condensation - the latter i ndependently of nuclear membranes, However, lamina disassembly is not affec ted, as judged by immunological analyses of A/C- and B-type lamins, In cont rast, immunoblocking of HA95 bound to condensed chromosomes does not impair chromatin decondensation, nuclear membrane reassembly or lamina reformatio n. Our results argue for a role for HA95 in anchoring nuclear membranes and lamins to chromatin in interphase, and in releasing membranes from chromat in at mitosis. The data also suggest that KA95 is not involved in initial b inding of membranes to chromatin upon nuclear reassembly. We propose that H A95 is a central platform at the chromatin/nuclear matrix interface implica ted in regulating nuclear envelope-chromatin interactions during the cell c ycle.