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Biochemistry Seminar – Jung-Hyun Min: “Structure and dynamics of DNA damage recognition by Rad4 nucleotide excision repair protein complex”
October 17, 2018 @ 4:00 pm - 5:00 pm
Department of Chemistry and Biochemistry
Title: “Structure and dynamics of DNA damage recognition by Rad4 nucleotide excision repair protein complex”
Abstract: DNA damage repair is central to maintaining the genome integrity and preventing cancer. The first step in DNA damage repair is the recognition of damaged sites from predominantly normal DNA. This task is especially formidable for the nucleotide excision repair (NER) which repairs structurally diverse lesions caused by various genotoxic sources such as UV irradiation, industrial pollutants and cigarette smoking. A key lesion recognition factor in the global genome NER is the xeroderma pigmentosum C (XPC) complex; it detects diverse NER lesions embedded within predominantly normal DNA before recruiting downstream factors. Mutations in the XPC gene can lead to the xeroderma pigmentosum cancer predisposition syndromes in humans. Despite extensive research, the fundamental mechanism underlying the versatile damage detection by XPC remains elusive. Here we present a multidisciplinary approach that combines X-ray crystallography and time-resolved fluorescence measurements, which allows us to map the trajectory of lesion recognition by the protein in high structural and temporal resolutions. Based on our recent studies on the yeast XPC ortholog, Rad4, we propose that Rad4/XPC may use a unique kinetics-based mechanism (‘kinetic gating’) in a multi-step process to recognize diverse NER lesions.
Host: Dorothy Shippen
Location: 108 Biochemistry Building (Bldg#1507)