Princeton University
Department of Molecular Biology

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Tiger Talks


Groundbreaking Telomere Research

Thu, Oct 25, 2012
Location - TBA


Professor of Molecular Biology


Professor Zakian started her talk by inviting over 700 students and teachers to share her journey in becoming a scientist. She stressed to the students that scientists can have a very enjoyable family life and are not just one-dimensional researchers. She shared numerous photos of herself growing up and of her own family and pets. Women with families can be successful in science. Dr. Zakian continued on to her favorite research topic, telomeres. We are born with 10,000 kb of telomeres. Most cells lose 50 – 100 bp with each cell division. DNA is made in a 5' to 3' direction and it is hard to replicate the end of a linear strand of DNA. Dr. Jim Watson recognized the problem of the lagging strand.

Dr. Elizabeth Blackburn, in Joe Gall's lab at Yale, while studying the micronucleus in Tetrahymena, found that the ends of chromosomes have a repetitive sequence CCCAA or C4A2. All vertebrates have C3TA2 repetitions that do not code for proteins. Carol Greider, a graduate student in Dr. Blackburn's lab discovered the activity that makes telomeres is telomerase. Telomerase is a combination of RNA and protein subunits. Why do telomeres shorten with each cell replication? Professor Zakian informed the students that as they sit there, their telomeres are getting shorter. One can estimate one's age by examining telomere length. Telomerase is not expressed in normal human cells, but is active in stem cells and cancer. Short telomeres are linked with numerous diseases. Humans with 50% of the normal level of telomerase die as young adults. Ninety percent of human tumors express telomerase.

The Zakian lab works with yeast. DNA helicase separates the strands of DNA and can also push proteins along DNA or RNA. Professor Zakian and her colleagues discovered Pif1 as a multi-functional helicase in yeast. Cells lacking Pif1 have long telomeres. Pif1 is an inhibitor of telomerase. Pif1 pushes telomerase off the end of the DNA. This protein sequence is conserved from bacteria to humans. Mutations in hPIF1 affect human health. A significant number of families with high rates of breast cancer do not have the genes knows to be linked to breast cancer.



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Howard Hughes Medical Institute

Princeton Center for Quantitative Biology