Figure 6.

Schematic showing 2 stages of cellular senescence in the response of PA1 cells to ETO, protective and destructive, and the relationship between NoA formation in the first, and release of heterochromatin fragments, in the second phase. These fragments originate from the nucleolus associated domains (NADs). It is hypothesized that dysfunction of the nucleolus in response to stress may lead to detention of DNA (cytosine-5)-methyltransferase 1 (DNMT1) in NoA, whose removal from targets in NADs activate retrotransposons resulting in fragmentation of pericentric heterochromatin and ultimate terminal disintegration of cell nuclei.