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Title: Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha]

Abstract

Budding yeast Cdc13-Stn1-Ten1 (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 Stn1-Ten1 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-like domain organization, the structures of Cdc13 OB 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 {alpha} (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 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.

Authors:
; ; ; ; ; ; ; ; ; ;  [1]
  1. Michigan-Med
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1023044
Resource Type:
Journal Article
Journal Name:
Cell Res.
Additional Journal Information:
Journal Volume: 21; Journal Issue: 02, 2011
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

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, Weill-Med), Nat. Yang-Ming), and UIUC). Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha]. United States: N. p., 2019. Web. doi:10.1038/cr.2010.138.
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, Weill-Med), Nat. Yang-Ming), & UIUC). Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha]. United States. doi:10.1038/cr.2010.138.
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, Weill-Med), Nat. Yang-Ming), and UIUC). Tue . "Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha]". United States. doi:10.1038/cr.2010.138.
@article{osti_1023044,
title = {Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha]},
author = {Sun, Jia and Yang, Yuting and Wan, Ke and Mao, Ninghui and Yu, Tai-Yuan and Lin, Yi-Chien and DeZwaan, Diane C. and Freeman, Brian C. and Lin, Jing-Jer and Lue, Neal F. and Lei, Ming and Weill-Med) and Nat. Yang-Ming) and UIUC)},
abstractNote = {Budding yeast Cdc13-Stn1-Ten1 (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 Stn1-Ten1 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-like domain organization, the structures of Cdc13 OB 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 {alpha} (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 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.},
doi = {10.1038/cr.2010.138},
journal = {Cell Res.},
number = 02, 2011,
volume = 21,
place = {United States},
year = {2019},
month = {2}
}

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