Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10065, USA.
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10065, USA
Genes Dev. 2023 Jul 1;37(13-14):555-569. doi: 10.1101/gad.350479.123. Epub 2023 Jul 26.
It has been known for decades that telomerase extends the 3' end of linear eukaryotic chromosomes and dictates the telomeric repeat sequence based on the template in its RNA. However, telomerase does not mitigate sequence loss at the 5' ends of chromosomes, which results from lagging strand DNA synthesis and nucleolytic processing. Therefore, a second enzyme is needed to keep telomeres intact: DNA polymerase α/Primase bound to Ctc1-Stn1-Ten1 (CST). CST-Polα/Primase maintains telomeres through a fill-in reaction that replenishes the lost sequences at the 5' ends. CST not only serves to maintain telomeres but also determines their length by keeping telomerase from overelongating telomeres. Here we discuss recent data on the evolution, structure, function, and recruitment of mammalian CST-Polα/Primase, highlighting the role of this complex and telomere length control in human disease.
几十年来，人们已经知道端粒酶可以延伸线性真核染色体的 3' 端，并根据其 RNA 中的模板来决定端粒重复序列。然而，端粒酶并不能减轻染色体 5' 端由于滞后链 DNA 合成和核酸酶处理而导致的序列丢失。因此，需要第二种酶来保持端粒完整：与 Ctc1-Stn1-Ten1（CST）结合的 DNA 聚合酶 α/引发酶。CST-Polα/引发酶通过填补反应来维持端粒，从而在 5' 端补充丢失的序列。CST 不仅通过阻止端粒酶使端粒过长来维持端粒，还通过控制端粒酶来决定端粒的长度。本文讨论了关于哺乳动物 CST-Polα/引发酶的进化、结构、功能和募集的最新数据，重点介绍了该复合物和端粒长度控制在人类疾病中的作用。
