The work in my laboratory concerns the synthesis and function of telomeres, the ends of eukaryotic chromosomes. Telomeric DNA consists of tandem repeats of very simple sequences, one strand of which is synthesized by the ribonucleoprotein enzyme telomerase. Telomerase specifies the sequence of telomeric DNA by using a short sequence within the telomerase RNA moiety as the template for DNA synthesis. Thus, telomeric DNA is unusual in being an essential chromosomal element synthesized by copying an RNA sequence; that is, by reverse transcription.
Our goal is to understand the mechanism of telomerase action and its impact on normal and diseased cells, such as cancer cells. One important question we wish to answer is the functions of the telomerase RNA and protein moieties of the enzyme; the RNA not only provides the template, but also has other essential functions. Specific RNA mutations destroy catalysis by telomerase, while others cause aberrant telomerase active site functions. An interesting question is whether telomerase represents a relic of an ancestral RNA enzyme or ribozyme. Our studies of telomere synthesis by telomerase in cells led to the finding that cell division is impaired by the actions of certain types of mutant telomerases. We seek to understand the full roles of telomerase in cell division processes. To this end, we are analyzing telomerases and telomeres in yeasts and in human cells. |
Blackburn, E.H. Switching and signaling at the telomere. Cell. 106 : 661-673 (2001).
Chan, S. and E.H. Blackburn. Telomerase and ATM/Tel1p protect telomeres from nonhomologous end joining. Molec Cell 11 :1379-1387 ( 2003 ).
Kim, M.M, L. Xu and E. H. Blackburn. Catalytically normal human telomerase mutants with allele-specific biological properties. Exper Cell Res 288 : 277-287 (2003).
Li, S., J.E. Rosenberg, A.A. Donjacour, I.L. Botchkina, Y.-K. Hom, G.R. Cunha and E.H. Blackburn. Rapid inhibition of cancer cell growth induced by lentiviral expression of mutant-template telomerase RNA constructs and anti-telomerase siRNA. Cancer Res 64 : 4833-4840 (2004).
Lin, J., H. Ly, A. Hussain, M. Abraham, S. Pearl, T.G. Parslow, Y. Tzfati and E.H. Blackburn. A universal telomerase RNA core structure includes structure motifs required for binding the telomerase reverse transcriptase protein. Proc Natl Acad Sci USA 101 :14713-8 (2004).
Epel, E.S., E.H. Blackburn, J. Lin, F. Dhabar, N. Adler, J. Morrow, and R. Cawthon. Accelerated telomere shortening in response to life stress.
Proc Natl Acad Sci U S A . 2004 Dec 7; 101 ( 49 ): 17312-5 . Epub 2004 Dec 1.
information last updated November 2004 |
Biomedical Sciences (BMS) Graduate Program
