Year: 2017
Type: article
Abstract: DNA polymerases (pols) play a pivotal role in both the replication and the repair of genomic DNA.Replicative pols are highly accurate and processive, synthesizing long stretches of DNA in a single binding event, while repair and bypass pols are error-prone and only able to synthesize incorporate a few nucleotides before dissociation.During replication, the pol may encounter DNA modifications induced caused by endogenous and exogenous factors such as oxidative metabolites, UV radiation, or epigenetic additions.These modifications may alter the local structure of DNA, resulting in inhibition of the replicative pol and stalling of the replication machinery.When the replicative pol stalls, a repair or bypass pol can take over and perform translesion synthesis (TLS).During TLS, a nucleotide is inserted opposite a lesion-containing base on the template DNA strand before the replicative pol can continue DNA synthesis.The mechanistic details of DNA replication, bypass, and repair are areas of ongoing research and are important to other areas of research such as drug design, cancer research, metabolism, and aging.The overarching goal of my research was to contribute to the mechanistic understanding of how pols perform DNA synthesis and bypass of DNA lesions.With this goal in mind, one of my main projects was to investigate the bypass kinetics of a common epigenetic signal, modification of the C5-position on cytosine (5xC).I used a specialized pol, human pol , to conduct this investigation.Using pre-steady state kinetic Dedication I would like to dedicate this document to the following people: To those of you who feel like impostors: You fill a unique space in the world.To those of you who feel like you're not good enough: Most standards are arbitrary-do not allow them to define you.To those of you fighting to be respected simply as a human being: Do not give up.v Acknowledgments I would like to acknowledge the many people whose help, both personal and professional, made this document and the journey leading up to it possible.I would like to thank my mother, Cindy Evers, for supporting me mentally, emotionally and physically for my entire academic career; for helping edit this document; and for teaching me by example the many characteristics I needed to embody to get this far: strength, wisdom, patience, confidence, grace, kindness, and respect.I would like to thank each of my former lab mates (and good friends) who helped me learn the basics of a biochemistry lab, helped me design experiments, and engaged me in scientific discussion: Varun
Author: Petra C. Wallenmeyer
Institution: The Ohio State University
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2889738700