Publication Date

2023

Document Type

Thesis

Committee Members

Michael G. Kemp, Ph.D. (Advisor); Ravi P. Sahu, Ph.D. (Committee Member); Yong-jie Xu, M.D., Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Cell cycle control, DNA repair, and cell survival have all been linked to the ataxia-telangiectasia and Rad3-related (ATR) kinase, a vital part of the DNA damage response system. In this work, we looked at the role of ATR kinase in human keratinocytes that were dormant and exposed to solar simulating light (SSL). Our findings demonstrated that SSL activates the ATR kinase, phosphorylating downstream substrates such as KAP1, Chk2, and H2AX. In addition, we noticed that quiescent keratinocytes exposed to SSL experienced a decrease in viability when ATR kinase activity was inhibited. Our research indicates that in quiescent keratinocytes exposed to SSL, ATR kinase is crucial for preserving cell viability and avoiding cell death. The creation of cutting-edge treatments for skin cancer and other conditions connected to the skin may be impacted by understanding the role of ATR kinase in this situation. The proposed effort is new since there are few studies exploring the activity of ATR kinase in quiescent human keratinocytes, whereas the majority of research has focused on proliferating or replicating cells. In addition, the majority of studies have employed UV light sources that emit mostly UVB wavelengths, whereas SSL light sources emit largely UVA wavelengths. Considering that the majority of cells in the human body are non-proliferating and in a quiescent state, this study has important implications for our understanding of the function of ATR kinase. To clarify the role of ATR kinase in quiescent cells and its possible influence on skin diseases, more study is necessary.

Page Count

63

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2023

ORCID ID

0009-0001-8348-0665

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