BEGIN:VCALENDAR VERSION:2.0 PRODID:researchseminars.org CALSCALE:GREGORIAN X-WR-CALNAME:researchseminars.org BEGIN:VEVENT SUMMARY:Lynn Zechiedrich (Baylor College of Medicine - USA) DTSTART:20211001T150000Z DTEND:20211001T160000Z DTSTAMP:20260423T022829Z UID:GEOTOP-A/4 DESCRIPTION:Title: Cooperativity of looping- and supercoiling-mediated base-pair disruption among distant sites modulates the 3-D structure of DNA to control its acti vity\nby Lynn Zechiedrich (Baylor College of Medicine - USA) as part o f GEOTOP-A seminar\n\n\nAbstract\nJonathan M. Fogg and Lynn Zechiedrich\n\ nBaylor College of Medicine\n\nDNA in cells is supercoiled and constrained into loops. Despite the ubiquity and importance of supercoiling in regula ting nearly every aspect of DNA activity\, relatively little is known abou t how. To determine how supercoiling influenced DNA shape\, we determined the 3-D structures of individual 336 bp DNA minicircles over a wide range of supercoiling from s = -0.019 to +0.085 (Irobalieva et al. 2015). Superc oiled DNA forms far more bent and contorted shapes than predicted. We soug ht to understand how DNA formed these shapes using coarse-grained molecula r dynamics simulations (Wang et al. 2017)\, which predicted that site-spec ific disruptions to base pairing may explain otherwise energetically unfav orable sharp DNA bends. Likewise\, bending strain at the apices of highly writhed DNA circles leads to broken base pairs. Probing for and mapping wh ere base-pair disruptions occur\, we discovered that negative supercoiling transmits mechanical stress along the DNA backbone to disrupt base pairin g at specific distant sites (Fogg et al. 2021). This unprecedented base-pa ir disruption cooperativity among distant sites localizes certain sequence s to superhelical apices to facilitate DNA writhing and relieve torsional strain\, likely preventing more extensive denaturation that can cause geno mic instability. We also discovered how cells may exploit DNA looping to p osition DNA nicks to facilitate repair. Our data explain how DNA can form short loops through base-pair disruption and reveal a complex interplay be tween looping- and supercoiling-mediated site-specific disruptions to base pairing and the 3-D conformation of DNA\, which influence how genomes are stored\, replicated\, transcribed\, repaired\, and likely other aspects o f DNA activity. We hope to harness these looping- and supercoiling-mediate d site-specific denaturation and mechanical correlations to design novel D NA shapes for nanotechnology.\n\nIrobalieva\, R.N.*\, Fogg\, J.M.*\, Catan ese\, D.J.\, Sutthibutpong\, T.\, Chen\, M.\, Barker\, A.K.\, Ludtke\, S.J .\, Harris\, S.A.\, Schmid\, M.F.\, Chiu\, W.\, and Zechiedrich\, L. (2015 ) Structural diversity of supercoiled DNA. Nature Comm. Oct 12\;6:8440 PMC 4608029 (*equal contribution)\n\nWang\, Q.\, Irobalieva\, R. N.\, Chiu\, W .\, Schmid\, M. F.\, Fogg\, J. M.\, Zechiedrich\, L.\, and Pettitt\, B.M. (2017) DNA sequence determines conformational distribution of minicircles under torsional stress. Nucleic Acids Res. 45\, 7633–7642 PMC5737869\n\n Fogg\, J.M.\, Judge\, A.K.\, Stricker\, E.\, Chan\, H.L.\, and Zechiedrich \, L. Supercoiling and looping promote DNA base accessibility and coordina tion among distant sites. Nature Comm. in press.\n LOCATION:https://researchseminars.org/talk/GEOTOP-A/4/ END:VEVENT END:VCALENDAR