CEPCEB Members
Constance I. Nugent
Assistant Professor
Department of Cell Biology and Neuroscience
University
of California, Riverside
Riverside, CA 92521
Phone: (951) 827-2383
Fax: (951) 827-3087
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Background I
earned my B.S. from the University of Wisconsin, Madison, with a major in Molecular
Biology, and my Ph.D. in 1995 from the University of Colorado in Boulder, CO for
my work on poliovirus assembly under the direction of Dr. Karla Kirkegaard. I
then joined Dr. Vicki Lundblad's lab at Baylor College of Medicine in Houston
as a postdoctoral fellow. My postdoctoral work made significant contributions
towards the definition of multiple genetic pathways and factors involved in telomere
function in the budding yeast S. cerevisiae. One pathway utilizes the enzyme telomerase
to compensate for terminal sequence loss by extending telomere sequence tracts.
Surprisingly, we found that factors such as MRE11, RAD50 and XRS2 that are involved
in DNA recombination processes such as NHEJ also function to promote telomere
extension by telomerase. Two additional genetic pathways are required to maintain
telomere integrity, and involve the yeast CDC13, STN1, TEN 1 genes and the YKU70
and YKU80 genes. Since joining the faculty at UCR as an Assistant Professor in
January of 2001, my lab has been continuing research to understand the dynamics
of telomere maintenance and replication throughout the cell cycle. Back
to Top  Telomeres
Telomeres, the physical ends of linear chromosomes, function to stabilize
chromosome ends. The telomeres of most eukaryotes are composed of short, repetitive
GT/CA sequence tracts that are complexed into a unique chromatin structure. The
terminal structure of telomeres is thought to act as a "cap" that protects
the chromosome ends from degradation and fusion with other chromosome ends. Since
the early work of Barbara McClintock and Hermann Muller that ascribed this protective
function to telomeres, many proteins and activities have been identified that
play important roles in maintaining telomeres. In addition, it has been discovered
that telomeres can form higher-order structures such as T-loops and G-quartets.
Of course, many questions remain regarding how these myriad factors function,
how they allow the cell to distinguish a chromosome end from a DNA double-strand
break, and how their activities are coordinated through cycles of cell division.
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| Figure 1. Telomeres are the physical ends of linear chromosomes.
The cartoon depicts a "fold-back" model for the terminal protein structure
at S. cerevisiae telomeres. |
The enzyme telomerase,
a ribonucleoprotein complex with reverse transcriptase activity, is required to
maintain sufficient length of the terminal repetitive sequences as cells proliferate.
This enzyme can append telomeric DNA sequences onto telomere ends to compensate
for terminal sequence loss that occurs during chromosomal DNA replication; in
the absence of telomerase, loss of telomere length can eventually limit cell proliferation.
Many species use telomerase to maintain telomere length, however, not all cell
types in multicellular organisms maintain active telomerase.
Figure 2. Cartoon depicting the telomerase enzyme extending
a chromosome 3' end, compensating for terminal sequence loss that occurs during
DNA replication. Telomerase contains an RNA subunit that functions as a template
for the reverse-transcriptase activity of the enzyme.
Figure from Greider
and Blackburn, Scientific American, Feb. 1996, pp. 92-97.
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The research in my lab is focused upon elucidating how telomere
integrity is maintained and how telomere length is regulated. We are currently
using the budding yeast S. cerevisiae as a model system to approach these questions.
One area of research within the lab is to understand at a molecular level how
the single-stranded telomere binding protein, Cdc13p, functions to maintain telomere
integrity. A second project is addressing the function of a protein that may be
involved in telomerase biogenesis or regulation. Our long-term goal is to understand
the processes that allow telomeres to mediate their protective chromosome capping
function throughout the cell cycle.
Back
to Top Selected
Publications Related to Telomeres (Bibliography
page)
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