Extra Credit Assignment

Stephanie Zeibak

10.13.15

Dr. Ribes

Extra Credit Assignment

John H. Blaffer lecture series at MD Anderson featured Dr. Vicki Lindblad in her lecture discussing “Maintaining Telomere Homeostasis: The Intersection Between Telomerase and DNA Replication”. Basic concepts that were introduced during the lecture and that should be known before continuing is what telomeres are, what telomerase is, and what is DNA replication. Telomeres, which are the ends of chromosomes, are important for genome stability and cell proliferation, telomerase is a ribonucleoprotein that adds a polynucleotide to the 3' end of telomeres, and DNA replication involves the process of producing two identical replicas from one original DNA molecule. All are basic concepts that are learned in our class. Another important fact learned from the lecture that is good to know is that maintaining telomere homeostasis relates to the maintenance of telomere length during DNA replication.

Dr. Lundblad began her lecture with describing what each of these basic concepts mean and how they are significant to her research. She then described how evidence has shown that defects in three telomere- related complexes- telomerase, shelterin, and t-RPA (a RPA- like complex), which is composed of cdc13, stn1, and ren1, can be the cause of organ failure in humans, as well as causing cancer, defected pancreatic cell, liver cirrhosis, bone marrow failure, and pulmonary fibrosis. Dr. Lundblad explained how the important function of the t-RPA complex is to prevent the collapse of the replication fork (found after the unwinding of DNA at the origin and synthesis of new strands) by modifying the DNA replication pathway to form a telomere- specific replisome (where DNA replication occurs). It is demonstrated that a telomere-bound protein called cdc13, found in the composition of t-RPA, is responsible for recruiting telomerase to the chromosome ends when the collapse of the replication fork occurs. This is to prevent the buildup of shortened ends after the collapse. To make sure this has actually happened, a few approaches are taken. One that I caught her explaining about is an assay that is designed to find the errors in replication that occur during a single cell cycle. She explains how this will be used to determine whether collapsed replication forks are elongated by telomerase or not. This approach (and the other two that I did not catch) is also helped by an assay that watches the sequence changes that happen in response to the errors. This method that she uses clarifies how the t-RPA complex works with the DNA replication pathway to ensure telomere homeostasis.