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

作　　者：Jia Sun Yuting Yang Ke Wan Ninghui Mao Tai-Yuan Yu Yi-Chien Lin Diane C DeZwaan Brian C Freeman Jing-Jer Lin Neal FLue Ming Lei 

机构地区：[1]Howard Hughes Medical Institute [2]Department of Biological Chemistry, University of Michigan Medical School 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA [3]Department of Microbiology & Immunology, W.R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA [4]Institute of Biopharmaceutical Sciences, National Yang-Ming University, Shih-Pai 112, Taipei [5]Department of Cell and Developmental Biology, University of Illinois, 601 South Goodwin Avenue, Urbana, 1L 61801, USA

出　　处：《Cell Research》2011年第2期258-274,共17页细胞研究（英文版）

摘　　要：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.

关 键 词：TELOMERE POLYMERASE TELOMERASE 

分 类 号：Q78[生物学—分子生物学] TU391[建筑科学—结构工程]