Distinct 'safe zones' at the nuclear envelope ensure robust replication of heterochromatic chromosome regions

Chromosome replication and transcription occur within a complex nuclear milieu whose functional subdomains are beginning to be mapped out. Here we delineate distinct domains of the fission yeast nuclear envelope (NE), focusing on regions enriched for the inner NE protein, Bqt4, or the lamin interacting domain protein, Lem2. Bqt4 is relatively mobile around the NE and acts in two capacities. First, Bqt4 tethers chromosome termini and the mat locus to the NE specifically while these regions are replicating. This positioning is required for accurate heterochromatin replication. Second, Bqt4 mobilizes a subset of Lem2 molecules around the NE to promote pericentric heterochromatin maintenance. Opposing Bqt4-dependent Lem2 mobility are factors that stabilize Lem2 beneath the centrosome, where Lem2 plays a crucial role in kinetochore maintenance. Our data prompt a model in which Bqt4-rich nuclear subdomains are 'safe zones' in which collisions between transcription and replication are averted and heterochromatin is reassembled faithfully.