Ph.D., University of California, San Francisco
Tel: (617) 552-3573
E-mail: anne.stellwagen.1@bc.edu
Fields of Interest
Telomeres, telomerase and chromosome stability
Academic Profile
My laboratory is interested in how cells preserve the integrity of their chromosomes. The ends of linear chromosomes pose a particular problem, because they must be differentiated from broken DNA
ends that result from DNA damage. Most eukaryotes solve this problem by encasing their chromosome ends in protective protein: DNA structures, or telomeres. Telomeres hide the chromosome end from the
checkpoint proteins that survey the genome looking for DNA damage, and from the enzymes that degrade and repair broken DNA ends.
Telomeres are not impenetrable — they must transiently open to allow
telomerase to gain access to the chromosome end. Telomerase is the enzyme that
adds new telomeric DNA onto the ends of chromosomes. This activity is important
for dividing cells to maintain their chromosomes at full length, because conventional
DNA polymerases cannot replicate the very ends of linear DNA molecules. In humans,
telomerase is turned off in most terminally differentiated cells, but telomerase
is reactivated in most types of tumors, and this reactivation correlates with
the ability of tumor cells to proliferate indefinitely. Therefore, understanding
how telomerase activity is regulated is of great interest to cancer biologists.
We are studying telomerase function and regulation in a model organism that proliferates continuously, the budding yeast Saccharomyces cerevisiae. We use genetic and biochemical approaches to
investigate how the RNA and protein components of telomerase assemble, how telomerase associates with telomere binding proteins, and how these interactions change over the course of the cell cycle.
We have also uncovered a mechanism that enables telomerase to be recruited to damaged DNA, where it caps off the broken chromosome by adding a telomere. This is a crude and potentially risky form of
DNA repair, because the DNA on the other side of the break is lost, but telomere healing does enable the checkpoint to be released and the cell to resume growth. We are comparing telomerase action at
native versus broken DNA ends, identifying factors that regulate whether telomere healing occurs, and investigating what types of DNA damage depend on this mechanism of DNA repair.
Representative Publications
Stellwagen, A. E., Haimberger, Z.W., Veatch J. R., and Gottschling, D. E. 2003.
Ku interacts with telomerase RNA to promote telomere addition at native and
broken chromosome ends. Genes & Development 17: 2384–2395.
Peterson, S. E. , Stellwagen, A.E., Diede, S. J., Singer, M. S., Haimberger,
Z. W., Johnson, C. O., Tzoneva, M., and Gottschling, D. E. 2001. The function
of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku. Nature
Genetics 27: 64–67. (link
to PubMed abstract)
DuBois, M. L., Diede, S. J., Stellwagen, A. E., and Gottschling, D. E. 2001.
All things must end: telomere dynamics in yeast. Cold Spring Harbor Symposium
on Quantitative Biology 65: 281–296. (link
to PubMed abstract)
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