Publication Date

2021

Document Type

Thesis

Committee Members

Michael G. Kemp, Ph.D. (Advisor); Jeffrey B. Travers, Ph.D., M.D. (Committee Member); Yong-Jie Xu, Ph.D., M.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

The functions of Ataxia telangiectasia and Rad-3 related protein (ATR) is very much important in a cell, as it is a DNA damage response protein, which plays an important role in cell division, DNA repair and apoptosis. This protein helps in proliferation in the actively DNA dividing normal cells and in cancer cells. The functions of ATR in a proliferating cell are well studied and known to involve regulation of replication fork and cell cycle progression after DNA damage. Whereas, in a non-replicating cell, the functions of ATR are not so well known. In the human body, most of the cells are in a non-replicating state, which do not actively replicate DNA, and include cells in a quiescent, senescent, and terminally differentiated state. What could be the function of ATR in these cells is something that nobody has ever looked at and is important because differentiated cells are routinely exposed to DNA damaging agents. ATR inhibitors are used as combination treatments in DNA damage-based anti-cancer therapies to inhibit pro-survival functions of ATR in cancer cells. Some of the studies show that, inhibition of ATR in non-diving cells would show an opposite effect than in the diving cells in response to DNA Damage caused by UVB. Hence, we have conducted experiments to test if inhibition of ATR would show a pro-survival role in differentiated keratinocytes. DNA damage has been induced using UV-B radiation and ATR is activated in both differentiated N-TERT keratinocytes in vitro and in human skin.

Page Count

64

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2021

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

ORCID ID

0000-0003-3517-824X


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