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Title: Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions

Telomerase helps maintain telomeres by processive synthesis of telomere repeat DNA at their 3'-ends, using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). In this paper, we report the cryo–electron microscopy structure of Tetrahymena telomerase at ~9 angstrom resolution. In addition to seven known holoenzyme proteins, we identify two additional proteins that form a complex (TEB) with single-stranded telomere DNA-binding protein Teb1, paralogous to heterotrimeric replication protein A (RPA). The p75-p45-p19 subcomplex is identified as another RPA-related complex, CST (CTC1-STN1-TEN1). This study reveals the paths of TER in the TERT-TER-p65 catalytic core and single-stranded DNA exit; extensive subunit interactions of the TERT essential N-terminal domain, p50, and TEB; and other subunit identities and structures, including p19 and p45C crystal structures. Finally, our findings provide structural and mechanistic insights into telomerase holoenzyme function.
Authors:
 [1] ;  [2] ;  [2] ;  [2] ;  [3] ;  [4] ;  [5] ;  [2] ;  [4] ;  [6] ;  [7] ;  [8]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. Dept. of Microbiology, Immunology, and Molecular Genetics. California Nanosystems Inst.
  2. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry
  3. Univ. of California, Los Angeles, CA (United States). Dept. of Biological Chemistry
  4. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
  5. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. UCLA-U.S. Dept. of Energy (DOE) Inst. of Genomics and Proteomics
  6. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. Dept. of Biological Chemistry. UCLA-U.S. Dept. of Energy (DOE) Inst. of Genomics and Proteomics
  7. Univ. of California, Los Angeles, CA (United States). Dept. of Microbiology, Immunology, and Molecular Genetics. California Nanosystems Inst.
  8. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. California Nanosystems Inst. UCLA-U.S. Dept. of Energy (DOE) Inst. of Genomics and Proteomics
Publication Date:
OSTI Identifier:
1226366
Grant/Contract Number:
AC02-06CH11357; FC03-02ER63421; GM048123; MCB1022379; GM071940; GM103479; R01GM054198; 14POST18870059; GM101874; GM007185; DGE-1106400; S10RR23057; S10OD018111; DBI-133813; P41 RR015301; P41 GM103403
Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 350; Journal Issue: 6260; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Research Org:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Org:
USDOE; National Inst. of Health (NIH) (United States); National Science Foundation (NSF); American Heart Association (United States)
Contributing Orgs:
Univ. of California, Berkeley, CA (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES