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Telomerase and the Consequences of Telomere Dysfunction

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Uploaded on Dec 7, 2010

Air date: Wednesday, December 01, 2010, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Category: Wednesday Afternoon Lectures
Description: Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase that synthesizes telomere sequences de novo onto chromosome ends. Telomerase is specialized reverse transcriptase, requiring both a catalytic protein and an essential RNA component. In the absence of telomerase, telomeres shorten progressively as cells divide, and telomere function is lost. For this reason, telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. The Greider lab is focused understanding telomerase and cellular and organismal consequences of telomere dysfunction. We use biochemistry, yeast and mice to examine telomere function. We generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. In the later generations, when telomeres are short, cells die via apoptosis or senescence. Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. We also are using our telomerase null mice to explore the role of telomerase stem cells and aging. In human families, Telomerase mutations cause autosomal dominant dyskeratosis congenita and the associated bone marrow failure. We have developed a strain of mice that are haploinsufficient for telomerase and show many hallmarks of dyskeratosis congenita and age related degenerative disease. Our lab is focused on understanding how short telomeres cause these diseases as well as the mechanisms that regulate telomere length equilibrium.

Lecture Objectives:
1. Understand the role of telomerase in telomere length
2. Understand the effect of short telomeres in cancer cell growth
3. Discuss role of telomere shortening in age related disease

The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.
Author: Carol Greider, Ph.D., Nobel Laureate, Johns Hopkins School of Medicine
Runtime: 00:58:07
Permanent link: http://videocast.nih.gov/launch.asp?1...

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