Cells unravel their centromeres as they enter senescence, Swanson et al. reveal.
Senescent cells are metabolically active but no longer capable of dividing. This permanent exit from the cell cycle can be induced by the telomere shortening associated with aging or by other stresses such as the expression of active oncogenes. Despite the importance of senescence for both aging and tumor suppression, however, researchers have failed to identify any cellular markers that are common to all types of senescent cell. Some human fibroblasts, for example, form compact heterochromatin foci called SAHFs as they enter senescence. But SAHFs aren’t formed in mouse fibroblasts or in cells from patients with the premature aging disease Progeria, suggesting that there is not a unifying mechanism of cellular senescence.
Swanson et al. found that the satellite DNA found at human and mouse centromeres unraveled from its normal compact state as cells entered senescence. This unraveling—which the researchers termed senescence-associated distension of satellites, or SADS—occurred regardless of how senescence was induced and appeared to occur early in the process of cell cycle exit. SADS weren’t formed in immortal, transformed cell lines. Nor were they seen in cancer cells in vivo, with the exception of a benign prostate tumor whose cells were senescent. Strikingly, cells from Progeria patients formed SADS as they exited the cell cycle, suggesting that these prematurely arrested cells follow the same senescence pathway as normally aging cells.
The satellites unraveled to a far greater extent than seen during ordinary chromosome decondensation. Indeed, there was no change in the levels of several histone modifications associated with compact heterochromatin. SADS therefore reflects a unique higher order unfolding of chromatin, which, say the authors, occurs at structures critical for cell division and could thus prove key to preventing proliferation.
Text by Ben Short