All living cells perform DNA replication through a group of enzymes called DNA polymerases. Unfortunately, DNA is constantly exposed to external and internal agents capable of causing damage. DNA damage causes blocks to replication that can be overcome through a special class of DNA polymerases, called the Y-family polymerases; which are able to traverse DNA lesions. Cisplatin is a common chemotherapeutic agent that damages DNA and has been used to treat cancer. However, many patients become resistant to cisplatin. The chemoresistance to cisplatin treatment is due in part to damage bypass performed by the specific Y-family polymerase, polymerase eta. The potential role of Y-family DNA polymerases in the pathway of chemotherapeutic resistance offers a novel target for inhibition.
To cultivate this thesis, I will provide a brief introduction of cancer and how DNA plays a role in the development of the disease. I will then discuss the various types of DNA damage and how they affect the replication process resulting in mutagenesis. Following that, I will begin discussing several types of repair processes that our cells have adopted to tolerate DNA damage. This will lead me to hone in one specific mechanism called translesion synthesis, and discuss how through the recruitment of a special class of DNA polymerases called the Y family polymerases allows for DNA replication to continue without fixing the damage, and how this plays a role in chemotherapeutic resistance. From this I will get into the specifics of my project, centered on DNA polymerase eta’s role in cisplatin resistance which led to implementation of a high-throughput screening assay to identify potential small molecule targets against Y-family polymerase eta. I will conclude by summarizing the overall significance of the work done, and discuss research work that is currently being done on the inhibition of Y-family polymerases, as well as conclude with what future work can be done regarding this project.
Samer Lone (Thesis Advisor)
Copyright and Permissions
Original document was submitted as an Honors Program requirement. Copyright is held by the author.
Bryson, Keri. (2018). Development of a High-throughput Screening Assay for Potential Inhibitors Against DNA Polymerase Eta. In BSU Honors Program Theses and Projects. Item 298. Available at: http://vc.bridgew.edu/honors_proj/298
Copyright © 2018 Keri Bryson