Overcoming steric hindrances during replication of peripheral heterochromatin

Due to a tight attachment of peripheral heterochromatin to the nuclear lamina its replication is connected with inevitable topological hindrances. Additional hindrances are caused by high stability of the lamina that complicates the access of replication factors to DNA duplication sites under conditions of highly condensed matrix with limited mobility. The work focuses on detailed study of structural organization and dynamics of the lamina in respect to replication of peripheral heterochromatin that is attached to it. The study of mobile properties of lamins at various stages of the S-phase using live cell imaging and super-resolution microscopy showed the absence of the dependence of lamins’ mobility on replicative status of attached heterochromatin. These data confirm the hypothesis on regulation of linkage between chromatin and lamina at the level of molecular intermediates. It has been shown at the ultrastructural level that possible temporary disruption in molecular bonds between the lamina and peripheral chromatin during replication does not cause movement of replicated domains from the nuclear periphery.