Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase a

Budding yeast Cdc13-Stnl-Tenl （CST） complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A （RPA）-like complex. Previous genetic and structural studies revealed a close resemblance between Stnl-Tenl and RPA32-RPA14...

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Bibliographic Details
Published in:Cell research 2019-02, Vol.21 (2), p.258-274
Main Authors: Sun, Jia, Yang, Yuting, Wan, Ke, Mao, Ninghui, Yu, Tai-yuan, Lin, Yi-chien, Dezwaan, Diane C, Freeman, Brian C, Lin, Jing-jer, Lue, Neal F, Lei, Ming
Format: Article
Language:English
Subjects:
DNA聚合酶
二聚化
亚基相互作用
催化亚基
端粒长度
结构基础
芽殖酵母
蛋白A
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Summary:Budding yeast Cdc13-Stnl-Tenl （CST） complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A （RPA）-like complex. Previous genetic and structural studies revealed a close resemblance between Stnl-Tenl and RPA32-RPA14. However, the relationship between Cdc13 and RPA70, the largest subunit of RPA, has remained unclear. Here, we report the crystal structure of the N-terminal OB （oligonucleotide/oligosaccharide binding） fold of Cdc13. Although Cdc13 has an RPA70-1ike domain organization, the structures of Cdc130B folds are significantly different from their counterparts in RPA70, suggesting that they have distinct evolutionary origins. Furthermore, our structural and biochemical analyses revealed unexpected dimerization by the N-terminal OB fold and showed that homodimerization is probably a conserved feature of all Cdc13 proteins. We also uncovered the structural basis of the interaction between the Cdc13 N-terminal OB fold and the catalytic subunit of DNA polymerase a （Poll）, and demonstrated a role for Cdc13 dimerization in Poll binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Poll interaction revealed multiple mechanisms by which dimerization regulates telomere lengths in vivo. Collectively, our findings provide novel insights into the mechanisms and evolution of Cdc13.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2010.138