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1篇 您的检索式：作者名="Futang Wan"

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		题名	作者	年代	出处	被引量
	1	Zipper head mechanism of telomere synthesis by human telomerase显示文摘Telomerase,a multi-subunit ribonucleoprotein complex,is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment of its own RNA component as the template.Despite recent structural characterizations of human and Tetrahymena telomerase,it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA.Here,we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Åand 3.9 Åfor the catalytic core and biogenesis module,respectively.The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase(TERT)catalytic subunit functions as a zipper head to limit the length of the short primer–template duplex in the active center.Moreover,our structural and computational analyses suggest that TERT and telomerase RNA(hTR)are organized to harbor a preformed active site that can accommodate short primer–template duplex substrates for catalysis.Furthermore,our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase.We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary.Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis.In addition,we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases.Together,our study provides an integrated model for telomerase-mediated telomere synthesis.	Futang Wan Yongbo Ding Yuebin Zhang Zhenfang Wu Shaobai Li Lin Yang Xiangyu Yan Pengfei Lan Guohui Li Jian Wu Ming Lei	2021	Cell Research2021，31，12：	0

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