Stressed out: Probing DNA replication stress and the role of G-quadruplexes via stochastic process approaches

MirandaLynch

Univ. at Buffalo/Hauptman-Woodward Institute

"Stressed out: Probing DNA replication stress and the role of G-quadruplexes via stochastic process approaches"

Replication stress refers to the impeding of DNA copying and the slowing or arresting of replication forks during DNA synthesis. It arises due to a number of exogenous and endogenous agents such as reactive oxygen species (ROS), radiation-induced DNA lesions, and noncanonical folded DNA species such as G-quadruplexes. Replication stress can give rise to chromosomal missegregation in anaphase, DNA breakage, or faulty rearrangements. In this work, we take a stochastic process approach to modeling replication stress, using a coupled system of point processes to capture replication fork distribution and characterization of replication origin licensing, and Poisson process modeling of origin activation. Recent work in yeast has demonstrated the appropriateness of the Poisson model for capturing the stochastic multiple activation process under replication stress. Finally we focus particularly on the role of G-quadruplexes (G4), which are guanine (G)-rich regions of DNA that form noncanonical quadruple-stranded structures that are implicated in replication stress. We discuss how the different topologies of G4 potentially influence the origin activation process modeled in this work.
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