|
Telomeres
and Telomerase
My research program is on telomeres, the DNA-protein complexes at the
ends of linear chromosomes in eukaryotes that protect chromosome ends,
and on the enzyme telomerase. We discovered previously that telomeric
DNA is synthesized by a ribonucleoprotein enzyme, telomerase. A short
template sequence in the RNA of telomerase is copied into telomeric DNA.
This work established that telomerase is a specialized reverse transcriptase
of normal cells. However, the integral RNA of telomerase also plays key
roles in enzyme action. We are studying how telomerase activity is built
up from this novel collaboration between telomerase protein and RNA. We
have demonstrated that certain telomerase RNA mutants cause telomere shortening
and cellular senescence in the ciliated protozoan Tetrahymena,yeasts,and
human cells in culture, and that chemical inhibitors of telomerase caused
human cell telomeres to shorten. Other mutations of telomeres can cause
cells to stop dividing in anaphase in the cell cycle, or cause apoptosis
ofhuman cells. We want to determine the mechanism of telomere capping
that normally prevents aberrant chromosome behavior. We are currently
testing the application of these findings for an anti-cancer strategy.
Finally, telomerase also affects cells in ways beyond its role in polymerization
of telomeric DNA. We are using yeast and human cells to study these roles
of telomerase.
Selected Publications:
Tzfati, Y., T.B. Fulton, J. Roy, and E.H. Blackburn. Template boundary
in a yeast telomerase specified by RNA structure. Science. 288(5467):863-7
(2000).
Blackburn, E.H. Switching and signaling at the telomere. Cell. 106: 661-673
(2001).
Kim. M.M., M.A. Rivera, I.L. Botchkina, R. Shalaby, A.D. Thor, and E.H.
Blackburn. A low threshold level of expression of mutant-template telomerase
RNA is sufficient to inhibit human tumor cell growth. Proc. Natl. Acad.
Sci. U.S.A. 98:7982-7987 (2001).
Contact Information:
Email: telomer@itsa.ucsf.edu
Phone: 415/ 476-4912
Address: Box 2200, Genentech Hall Room S 312 F
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
|
