Publication Date

2017-04-14

Availability

Open access

Embargo Period

2017-04-14

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2015-10-16

First Committee Member

Feng Gong

Second Committee Member

Thomas K. Harris

Third Committee Member

Ralf Landgraf

Fourth Committee Member

Xin-Hai Pei

Abstract

The choice of DNA repair pathway and the subsequent initiation of a select pathway in response to a DNA lesion are complex, and many questions remaining as to their regulation. We identified the deubiquitinase OTU deubiquitinase 4 (OTUD4) as a novel putative interactor of Xeroderma pigmentosum complementation group C protein (XPC), one of the crucial sensors of DNA damage in global genome nucleotide excision repair (GG-NER). The goal of this study was to establish a greater understanding of the role of OTUD4 in the DNA damage response. While the complexity of the structure and function of OTUD4 remain to be fully unraveled, our study found that knockout of OTUD4 led to altered XPC ubiquitination and, intriguingly, to a specific sensitivity to cisplatin. Further studies will allow more understanding of the role of OTUD4 in the DNA damage response.

Keywords

OTUD4; XPC; DNA damage response; ubiquitination; nucleotide excision repair

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