Satellite distension in relation to other events in the cell senescence process. (A) In nuclei of cycling cells, the peri/centromeric satellite DNA signals are tightly compacted, but dramatically distend in senescent cells. This occurs before and irrespective of the later formation of SAHF, and in some cells within 48 h of the last S phase. SADS is seen in essentially all noncycling cells and occurs in cells that first up-regulate either the p21 or p16 pathway. In late stage senescence, both pathways are up-regulated, and the p16 pathway promotes formation of SAHF. During this process there is a reorganization of several heterochromatin factors as seen by immunofluorescence including H3K9Me3 and HP1γ, whereas H1 levels uniformly decrease with the formation of SAHF. Whereas nuclear diameter increases progressively and is most pronounced in cells with SAHF, SADS are seen in some cells before nuclear enlargement. The nuclear lamina protein (LaminB1) may play a role in the higher-order folding of the DNA as it is diminished in most cells before SADS form. (B) Sat DNA in cycling cells is tightly packaged and this packaging is lost during senescence as the DNA distends. Because three canonical histone modifications remain unchanged during senescence the difference in DNA packaging may be attributed to changes in higher-order folding.