台湾大学Jing-Jer Lin团队提出了端粒结合蛋白Cdc13对DNA的动态缩短。 相关研究成果于2021年4月8日发表在《美国化学会杂志》。

端粒对于染色体的维持是必不可少的。Cdc13是一种单链端粒DNA结合蛋白，在酵母中可覆盖端粒并调节端粒酶功能。尽管Cdc13与端粒DNA的特异性结合是端粒保护的关键，但Cdc13-DNA复合物保护端粒的具体机制尚不清楚。

利用两种单分子方法，即栓系粒子运动和原子力显微镜，研究人员证明了Cdc13与单链端粒DNA的特异性结合，使双链DNA缩短到不同的状态，碱基对相差70～80个。Cdc13的DNA缩短是动态的，且与双链DNA序列或长度无关。

值得注意的是，研究人员发现Pif1解旋酶不能从缩短的DNA-Cdc13复合物中去除Cdc13，表明Cdc13通过缩短结合的DNA形成了结构稳定的复合物。

总之，研究数据证实了Cdc13缩短了DNA的长度，并为缩短的DNA-Cdc13复合物有效保护端粒末端提供了证据。

附：英文原文

Title: Dynamic DNA Shortening by Telomere-Binding Protein Cdc13

Author: Yi-Yun Lin, Min-Hsuan Li, Yen-Chan Chang, Peng-Yu Fu, Ryosuke L. Ohniwa, Hung-Wen Li, Jing-Jer Lin

Issue&Volume: April 8, 2021

Abstract: Telomeres are essential for chromosome maintenance. Cdc13 is a single-stranded telomeric DNA binding protein that caps telomeres and regulates telomerase function in yeast. Although specific binding of Cdc13 to telomeric DNA is critical for telomere protection, the detail mechanism how Cdc13-DNA complex protects telomere is unclear. Using two single-molecule methods, tethered particle motion and atomic force microscopy, we demonstrate that specific binding of Cdc13 on single-stranded telomeric DNA shortens duplex DNA into distinct states differed by ～70–80 base pairs. DNA shortening by Cdc13 is dynamic and independent of duplex DNA sequences or length. Significantly, we found that Pif1 helicase is incapable of removing Cdc13 from the shortened DNA-Cdc13 complex, suggesting that Cdc13 forms structurally stable complex by shortening of the bound DNA. Together our data identified shortening of DNA by Cdc13 and provided an indication for efficient protection of telomere ends by the shortened DNA-Cdc13 complex.

DOI: 10.1021/jacs.1c00820

Source: https://pubs.acs.org/doi/10.1021/jacs.1c00820