BEGIN:VCALENDAR VERSION:2.0 METHOD:PUBLISH PRODID:-//Missouri State University/Calendar of Events//EN CALSCALE:GREGORIAN X-WR-TIMEZONE:America/Chicago BEGIN:VTIMEZONE TZID:America/Chicago BEGIN:DAYLIGHT TZOFFSETFROM:-0600 TZOFFSETTO:-0500 DTSTART:20070311T020000 RRULE:FREQ=YEARLY;BYMONTH=3;BYDAY=2SU TZNAME:CDT END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:-0500 TZOFFSETTO:-0600 DTSTART:20071104T020000 RRULE:FREQ=YEARLY;BYMONTH=11;BYDAY=1SU TZNAME:CST END:STANDARD END:VTIMEZONE BEGIN:VEVENT UID:88dd0657-539b-4bb1-abee-8aa071264511.231885@calendar.missouristate.edu CREATED:20231023T142444Z LAST-MODIFIED:20231023T142444Z LOCATION:Meyer Library\, Duane G. 101 SUMMARY:Chemistry & Biochemistry Seminar: "Visualizing Base Excision Repai r in Chromatin" DESCRIPTION:By Dr. Bret Freudenthal\, University of Kansas Medical and Can cer Center\n\n\nGenomic DNA is continually exposed to endogenous and exog enous factors that promote DNA damage. Eukaryotic genomic DNA is packaged into nucleosomes\, which present a barrier to accessing and effectively repairing DNA damage. The mechanisms by which DNA repair proteins overcom e this barrier to repair DNA damage in the nucleosome and protect genomic stability is unknown. Here\, we determine how the base excision repair ( BER) endonuclease AP-endonuclease 1 (APE1) recognizes and cleaves DNA dam age in the nucleosome. Kinetic assays determine that APE1 cleaves solvent -exposed AP sites in the nucleosome with 3 - 6 orders of magnitude higher efficiency than occluded AP sites. A cryo-electron microscopy structure of APE1 bound to a nucleosome containing a solvent-exposed AP site reveal that APE1 uses a DNA sculpting mechanism for AP site recognition\, where APE1 bends the nucleosomal DNA to access the AP site. Notably\, addition al biochemical and structural characterization of occluded AP sites ident ify contacts between the nucleosomal DNA and histone octamer that prevent efficient processing of the AP site by APE1. These findings provide a ra tionale for the position-dependent activity of BER proteins in the nucleo some and suggests the ability of BER proteins to sculpt nucleosomal DNA d rives efficient BER in chromatin. X-ALT-DESC;FMTTYPE=text/html:<html><head><title></title></head><body><p>By Dr. Bret Freudenthal\, University of Kansas Medical and Cancer Center</p >\n<p>Genomic DNA is continually exposed to endogenous and exogenous fact ors that promote DNA damage. Eukaryotic genomic DNA is packaged into nucl eosomes\, which present a barrier to accessing and effectively repairing DNA damage. The mechanisms by which DNA repair proteins overcome this bar rier to repair DNA damage in the nucleosome and protect genomic stability is unknown. Here\, we determine how the base excision repair (BER) endon uclease AP-endonuclease 1 (APE1) recognizes and cleaves DNA damage in the nucleosome. Kinetic assays determine that APE1 cleaves solvent-exposed A P sites in the nucleosome with 3 - 6 orders of magnitude higher efficienc y than occluded AP sites. A cryo-electron microscopy structure of APE1 bo und to a nucleosome containing a solvent-exposed AP site reveal that APE1 uses a DNA sculpting mechanism for AP site recognition\, where APE1 bend s the nucleosomal DNA to access the AP site. Notably\, additional biochem ical and structural characterization of occluded AP sites identify contac ts between the nucleosomal DNA and histone octamer that prevent efficient processing of the AP site by APE1. These findings provide a rationale fo r the position-dependent activity of BER proteins in the nucleosome and s uggests the ability of BER proteins to sculpt nucleosomal DNA drives effi cient BER in chromatin. </p></body></html> DTSTART;TZID=America/Chicago:20231108T153500 DTEND;TZID=America/Chicago:20231108T162500 SEQUENCE:0 URL:https://chemistry.missouristate.edu/Seminars.htm CATEGORIES:Public,Alumni,Current Students,Faculty,Future Students,Staff END:VEVENT END:VCALENDAR