Dying of a bad overhang

Cells with shortening telomeres hit two successive barriers: they first stop dividing as they become senescent, and later undergo a cell death process termed crisis. Although crisis may, as suggested by others, be controlled by overall telomere length, Sheila Stewart, Ittai Ben-Porath, Robert Weinberg (Whitehead Institute, Cambridge, MA), and colleagues now blame the onset of senescence on a particular structure at the end of telomeres.

The important structure is a single-stranded overhang of G-rich residues at the 3′ end. The group demonstrates that overhang length of several hundred bases is maintained over many generations of cell divisions, but drops to fewer than 100 residues at senescence. Telomerase increased overhang length, which may account for its ability to delay senescence. Various cellular stresses caused minor shortening of the overhang—cumulative stresses may therefore shorten...