|Description||Dr. Razie Yousefi|
Postdoctoral Fellow, University of Texas Medical Branch
What Can We Learn from Computer Simulations of DNA Replication?
Abstract: DNA replication is a process during which a DNA molecule is copied into two identical DNA
molecules. DNA replication starts at specific locations called replication origins at which the double helix DNA molecule unwinds and opens up leading to formation of two forks moving bidirectionally. Aberrant DNA replication is a major source of mutation and genome abnormalities. Replication stress induced, for example, by genotoxic agents, may lead to fork stalling, DNA breaks, and mutations, which have been implicated in cancer development. In this work, we first construct a computer model of DNA replication that includes variation in fork
velocities, which have been observed experimentally, but are absent in previous models. In addition, we study different models for the timing of replication initiation. Experimental data are used to select the best model to fit it on the timing of replication and fork speed. We also discuss how such modeling can elucidate basic principles of replication fork movement. In the next step, we study the phenomenon of fork stalling. In our model we assign probabilities of fork stalling to both regular sites and replication fork barriers (RFBs), which are specific sites that are more prone to fork stalling. Sequencing data are used to inform such modeling. Finally, we study the kinetics of DNA replication in the presence of hydroxyurea (HU), a DNA replication inhibitor. Our model suggests that HU slows down the kinetics of DNA replication. Experimental data is used to inform modeling. These together offer insights about the kinetics of replication in both normal and stress conditions.
Bio: Razie Yousefi is a postdoc fellow in biophysics and bioinformatics at UTMB. She received her master's degree from National University in Iran, and her PhD in physics from Baylor University. After her PhD, she
joined Dr. Rowicka's lab in computational biology where she has been studying biological systems by computer simulations and modeling. She recently collaborated on a couple of manuscripts in bioinformatics submitted to
high-impact-factor journals including Nature. Her project mainly concentrates on DNA replication under stress conditions to understand the mechanism of replication. She currently resides in Galveston with her husband,
Ahmad, and their dog, Hatchi.
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