Telomere Checkpoint in Development and Aging

The maintenance of genome integrity through generations is largely determined by the stability of telomeres. Increasing evidence suggests that telomere dysfunction may trigger changes in cell fate, independently of telomere length. Telomeric multiple tandem repeats are potentially highly recombinogenic. Heterochromatin formation, transcriptional repression, the suppression of homologous recombination and chromosome end protection are all required for telomere stability. Genetic and epigenetic defects affecting telomere homeostasis may cause length-independent internal telomeric DNA damage. Growing evidence, including that based on Drosophila research, points to a telomere checkpoint mechanism that coordinates cell fate with telomere state. According to this scenario, telomeres, irrespective of their length, serve as a primary sensor of genome instability that is capable of triggering cell death or developmental arrest. Telomeric factors released from shortened or dysfunctional telomeres are thought to mediate these processes. Here, we discuss a novel signaling role for telomeric RNAs in cell fate and early development. Telomere checkpoint ensures genome stability in multicellular organisms but aggravates the aging process, promoting the accumulation of damaged and senescent cells.

Automated summary

The stability of telomeres plays a crucial role in maintaining genome integrity across generations. Telomere dysfunction can lead to changes in cell fate, regardless of telomere length. The multiple tandem repeats in telomeres have the potential for recombination. Telomere stability requires heterochromatin formation, transcriptional repression, suppression of homologous recombination, and chromosome end protection. Genetic and epigenetic defects affecting telomere homeostasis can cause length-independent internal telomeric DNA damage. Telomeres, regardless of their length, serve as primary sensors of genome instability and can trigger cell death or developmental arrest. Telomeric RNAs have been found to play a signaling role in cell fate and early development. The telomere checkpoint mechanism ensures genome stability but accelerates the aging process.