title: Structure of the human telomeric Stn1-Ten1 capping complex.
abstract: The identification of the human homologue of the yeast CST in 2009 posed a new challenge in our understanding of the mechanism of telomere capping in higher eukaryotes. The high-resolution structure of the human Stn1-Ten1 (hStn1-Ten1) complex presented here reveals that hStn1 consists of an OB domain and tandem C-terminal wHTH motifs, while hTen1 consists of a single OB fold. Contacts between the OB domains facilitate formation of a complex that is strikingly similar to the replication protein A (RPA) and yeast Stn1-Ten1 (Ten1) complexes. The hStn1-Ten1 complex exhibits non-specific single-stranded DNA activity that is primarily dependent on hStn1. Cells expressing hStn1 mutants defective for dimerization with hTen1 display elongated telomeres and telomere defects associated with telomere uncapping, suggesting that the telomeric function of hCST is hTen1 dependent. Taken together the data presented here show that the structure of the hStn1-Ten1 subcomplex is conserved across species. Cell based assays indicate that hTen1 is critical for the telomeric function of hCST, both in telomere protection and downregulation of telomerase function.
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bryan
authors.forename: Cory
authors.initials: C
authors.lastname: Rice
authors.forename: Michael
authors.initials: M
authors.lastname: Harkisheimer
authors.forename: David C
authors.initials: DC
authors.lastname: Schultz
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Skordalakes
mesh_terms: D006801:Humans; D011485:Protein Binding; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D017433:Protein Structure, Secondary; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C544946:Stn1 protein, human; D034501:Telomere-Binding Proteins; C544947:Ten1 protein, human