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Mechanisms of DNA damage access within the nucleosome during Base Excision Repair


EMSL Project ID
51738

Abstract

Despite the packaging of eukaryotic DNA into chromatin through repeating units known as the nucleosomes, it is constantly damaged via reactive oxygen species (ROS). 8oxo-guanine (8oxoG) is a common form of DNA damage resulting from the oxidation of guanine. If not repaired, 8oxoG is mutagenic, causing G to T transversion mutations that can initiate and promote genomic instability and ultimately human disease, such as cancer. The cells primary defense against 8oxoG is the base excision repair (BER) pathway. Two BER proteins involved in the initial recognition and removal of 8oxoG are 8oxoG DNA glycosylase 1 (OGG1) and apurinic/apyrimidinic endonuclease 1 (APE1). OGG1 and APE1 must find, access, and repair genomic DNA damage in complex chromatin structures, where the DNA is packaged into nucleosomes. To this end, the overarching goal of this proposal is to determine the structural basis for DNA damage recognition within the nucleosome by the base excision repair proteins OGG1 and APE1.

Project Details

Start Date
2020-11-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Bret Freudenthal
Institution
University of Kansas Medical Center

Team Members

Benjamin Ryan
Institution
University of Kansas Medical Center

Tyler Weaver
Institution
University of Kansas Medical Center

Nicholas Schnicker
Institution
University of Iowa

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory