In Saccharomyces cerevisae, the Pif1 family of helicases is represented by Pif1 and Rrm3. These helicases affect telomere replication and play roles in replication fork progression. Additionally, Pif1 has been shown to preferentially unwind DNA/RNA hybrids and to be able to resolve G-quadruplex structures. [Bochman, 2010]. Based on Pif1's preference for unwinding DNA/RNA hybrids, I propose that Pif1 and Rrm3 cooperatively remove RNA from highly transcribed genes and that they facilitate replication fork progression through highly transcribed genes. Recent work has established that telomeres are transcribed into long, noncoding RNA called TElomeric Repetitive RNA [TERRA] [Azzalin, 2007]. I propose that Pif1 family helicases are involved in removing TERRA from the ends of telomeres. To further examine the roles of the Pif1 helicase, I will perform a synthetic genetic analysis using the pif1-m2 allele to search for genes that are synthetically lethal with Pif1. Azzalin, C., Reichenbach, P., Khoriauli, L., Giulotto, E., Lingner, J. Telomeric Repeat- Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends. 2007. Science. 318: 798-801 Bochman, M.L., Sabouri, N., Zakian, V.A. 2010. Unwinding the functions of the Pif1 family of helicases. DNA Repair. (9):3 237-249.
The purpose of my project is to explore the roles of the Pif1 helicases, which unwind genes and help promote genome stability. I am also studying telomeric RNA, which sticks to the ends of chromosomes and helps regulate chromosome length. Genome stability and telomere length are key pathways in aging.