Telomeres are DNA-protein complexes that protect chromosome ends from degradation and fusion. The enzyme telomerase maintains telomeres. Most human somatic cells jack telomerase, resulting in telomere damage that is associated with aging and cancer. A model for telomere damage in human cells is C. elegans trt-1 mutants that lack telomerase, resulting in telomere damage and sterility. Telomere damage is worsened when trt-1 mutants are starved. Upon starvation, juvenile worms can enter the dauer pathway, resulting in a significantly extended lifespan. Does starvation cause stress that damages telomeres while the dauer path- way protects telomeres? To address this, trt-1 mutants with the dauer pathway either blocked or aberrantly activated will be examined for exacerbated telomere damage upon starvation. In addition, the possible role of longevity genes in regulating trt-1-mediated telomere damage will be assessed. Mutations in RecQ helicases cause premature aging diseases in humans, and accelerated telomere damage in C. elegans trt-1 mutants. The role of RecQ helicases in telomere damage in the absence of telomerase will be studied. This research seeks to probe the potential interactions between telomeres, aging, and cancers.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM072150-03
Application #
7324809
Study Section
Special Emphasis Panel (ZRG1-F08 (29))
Program Officer
Toliver, Adolphus
Project Start
2005-12-01
Project End
2008-02-29
Budget Start
2007-12-01
Budget End
2008-02-29
Support Year
3
Fiscal Year
2008
Total Cost
$6,865
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Lowden, Mia Rochelle; Meier, Bettina; Lee, Teresa Wei-Sy et al. (2008) End joining at Caenorhabditis elegans telomeres. Genetics 180:741-54