Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization.
Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization.
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DOI：
10.1038/s41580-021-00328-y
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Cech TR
中科院分区：
文献类型：
--
作者：
Lim CJ;Cech TR
哺乳动物端粒长度的调节对于染色体的封端以及维持基因组稳定性和细胞寿命至关重要。这个过程需要端粒蛋白复合物和核糖核蛋白端粒酶之间的协调，从而延长端粒DNA。端粒蛋白调节端粒结构，募集端粒酶到可接近的端粒，并协调新合成的端粒单链DNA尾转化为双链DNA。端粒维持功能障碍导致端粒缩短，从而导致人类疾病，包括骨髓衰竭、过早衰老和癌症。最近的研究提供了新的见解端粒相关的相互作用（端粒复制体），并揭示了新的挑战，为未来的端粒结构生物学的努力，由于端粒结构的动态性质和大量的结构，端粒的形式。在这篇综述中，我们讨论了最近确定的shelterin和CTC 1-STN 1-TEN 1（CST）复合物的结构，它们如何参与端粒复制和染色体封端的调节，以及它们的编码基因中的致病突变如何影响特定的功能。该领域的主要问题包括所有端粒组件如何相对于彼此组装以及如何实现不同端粒结构之间的切换。
The regulation of telomere length in mammals is crucial for chromosome end-capping and thus for maintaining genome stability and cellular lifespan. This process requires coordination between telomeric protein complexes and the ribonucleoprotein telomerase, which extends the telomeric DNA. Telomeric proteins modulate telomere architecture, recruit telomerase to accessible telomeres and orchestrate the conversion of the newly synthesized telomeric single-stranded DNA tail into double-stranded DNA. Dysfunctional telomere maintenance leads to telomere shortening, which causes human diseases including bone marrow failure, premature ageing and cancer. Recent studies provide new insights into telomerase-related interactions (the ‘telomere replisome’) and reveal new challenges for future telomere structural biology endeavours owing to the dynamic nature of telomere architecture and the great number of structures that telomeres form. In this Review, we discuss recently determined structures of the shelterin and CTC1–STN1–TEN1 (CST) complexes, how they may participate in the regulation of telomere replication and chromosome end-capping, and how disease-causing mutations in their encoding genes may affect specific functions. Major outstanding questions in the field include how all of the telomere components assemble relative to each other and how the switching between different telomere structures is achieved.
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