Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts

Spatial organisation of the genome within the nucleus can play a role in ma intaining the expressed or silent state of some genes [1]. There are distin ct addresses for specific chromosomes, which have different functional char acteristics, within the nuclei of dividing populations of human cells [2]. Here, we demonstrate that this level of nuclear architecture is altered in cells that have become either quiescent or senescent. Upon cell cycle exit, a gene-poor human chromosome moves from a location at the nuclear peripher y to a more internal site in the nucleus, and changes its associations with nuclear substructures. The chromosome moves back toward the edge of the nu cleus at a distinctive time after re-entry into the cell cycle. There is a 2-4 hour period at the beginning of G1 when the spatial organisation of the se human chromosomes is established, Lastly, these experiments provide evid ence that temporal control of DNA replication can be independent of spatial chromosome organisation. We conclude that the sub-nuclear organisation of chromosomes in quiescent or senescent mammalian somatic cells is fundamenta lly different from that in proliferating cells and that the spatial organis ation of the genome is plastic.