Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Int J Mol Sci. 2023 Nov 5;24(21):15979. doi: 10.3390/ijms242115979.
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 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.
通过世代维持基因组完整性在很大程度上取决于端粒的稳定性。越来越多的证据表明，端粒功能障碍可能会触发细胞命运的改变，而与端粒长度无关。端粒的多个串联重复序列具有潜在的高度重组能力。异染色质形成、转录抑制、同源重组抑制和染色体末端保护都需要端粒稳定。影响端粒动态平衡的遗传和表观遗传缺陷可能导致与长度无关的内部端粒 DNA 损伤。越来越多的证据，包括基于研究的证据，表明存在端粒检查点机制，该机制将细胞命运与端粒状态协调一致。根据这一设想，端粒，无论其长度如何，都充当基因组不稳定性的主要传感器，能够触发细胞死亡或发育停滞。从缩短或功能失调的端粒中释放的端粒因子被认为介导这些过程。在这里，我们讨论了端粒 RNA 在细胞命运和早期发育中的新的信号作用。端粒检查点确保了多细胞生物的基因组稳定性，但加剧了衰老过程，促进了受损和衰老细胞的积累。
