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Chromatinization modulates topoisomerase II processivity.
Lee, Jaeyoon; Wu, Meiling; Inman, James T; Singh, Gundeep; Park, Seong Ha; Lee, Joyce H; Fulbright, Robert M; Hong, Yifeng; Jeong, Joshua; Berger, James M; Wang, Michelle D.
Afiliación
  • Lee J; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA.
  • Wu M; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA.
  • Inman JT; Howard Hughes Medical Institute, Cornell University, Ithaca, NY, 14853, USA.
  • Singh G; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA.
  • Park SH; Howard Hughes Medical Institute, Cornell University, Ithaca, NY, 14853, USA.
  • Lee JH; Biophysics Program, Cornell University, Ithaca, NY, 14853, USA.
  • Fulbright RM; Biophysics Program, Cornell University, Ithaca, NY, 14853, USA.
  • Hong Y; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Jeong J; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA.
  • Berger JM; Department of Electrical and Computer Engineering, Cornell University, Ithaca, NY, 14853, USA.
  • Wang MD; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Nat Commun ; 14(1): 6844, 2023 10 27.
Article en En | MEDLINE | ID: mdl-37891161
Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress. While cellular processes constantly create varying torsional stress, how this variation impacts type IIA topoisomerase function remains obscure. Using multiple single-molecule approaches, we examined the torsional dependence of eukaryotic topoisomerase II (topo II) activity on naked DNA and chromatin. We observed that topo II is ~50-fold more processive on buckled DNA than previously estimated. We further discovered that topo II relaxes supercoiled DNA prior to plectoneme formation, but with processivity reduced by ~100-fold. This relaxation decreases with diminishing torsion, consistent with topo II capturing transient DNA loops. Topo II retains high processivity on buckled chromatin (~10,000 turns) and becomes highly processive even on chromatin under low torsional stress (~1000 turns), consistent with chromatin's predisposition to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / ADN-Topoisomerasas de Tipo II Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / ADN-Topoisomerasas de Tipo II Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido