Abstract

The aim of the research in this proposal is to understand the mechanisms of telomere function in eukaryotes. Telomeres are essential chromosomal elements which stabilize the ends of linear nuclear chromosomes and allow their complete replication. Much of the proposed work emphasizes the ciliated protozoans Tetrahymena and Euplotes, which, because of specific aspects of their biology, afford advantageous experimental systems for study of telomere, function. Telomere structure is highly conserved throughout eukaryotes, and findings made in one system are likely to be relevant to general questions of telomere function.
Specific aims are to 1) determine the function of the essential RNA of a novel ribonucleoprotein enzyme, telomerase, that synthesizes the G-rich strand of the simple repeated sequences that form the essential cis-acting components of telomeres, 2) determine what structural features of telomeric DNA are required for recognition by telomerase, and investigate the mechanism of de novo telomere formation that occurs in ciliate macronuclear differentiation and chromosome healing, 3) investigate the enzymes responsible for synthesis of the complementary C-rich telomeric strand. 4) study the mechanism of genomic rearrangements in ciliate development, using an in vitro reaction system we have developed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026259-23
Application #
6179085
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Carter, Anthony D
Project Start
1990-07-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
23
Fiscal Year
2000
Total Cost
$479,894
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Jay, Kyle A; Smith, Dana L; Blackburn, Elizabeth H (2016) Early Loss of Telomerase Action in Yeast Creates a Dependence on the DNA Damage Response Adaptor Proteins. Mol Cell Biol 36:1908-19
Xie, Zhengwei; Jay, Kyle A; Smith, Dana L et al. (2015) Early telomerase inactivation accelerates aging independently of telomere length. Cell 160:928-939
Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue (2015) Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science 350:1193-8
Rafelski, Susanne M; Viana, Matheus P; Zhang, Yi et al. (2012) Mitochondrial network size scaling in budding yeast. Science 338:822-4
Li, Shang; Makovets, Svetlana; Matsuguchi, Tetsuya et al. (2009) Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression. Cell 136:50-61
Makovets, Svetlana; Blackburn, Elizabeth H (2009) DNA damage signalling prevents deleterious telomere addition at DNA breaks. Nat Cell Biol 11:1383-6
Anderson, Carol M; Blackburn, Elizabeth H (2008) Mec1 function in the DNA damage response does not require its interaction with Tel2. Cell Cycle 7:3695-8
Seidel, Jeffrey J; Anderson, Carol M; Blackburn, Elizabeth H (2008) A novel Tel1/ATM N-terminal motif, TAN, is essential for telomere length maintenance and a DNA damage response. Mol Cell Biol 28:5736-46
Makovets, Svetlana; Williams, Tanya L; Blackburn, Elizabeth H (2008) The telotype defines the telomere state in Saccharomyces cerevisiae and is inherited as a dominant non-Mendelian characteristic in cells lacking telomerase. Genetics 178:245-57
Hsu, Min; McEachern, Michael J; Dandjinou, Alain T et al. (2007) Telomerase core components protect Candida telomeres from aberrant overhang accumulation. Proc Natl Acad Sci U S A 104:11682-7

Showing the most recent 10 out of 89 publications