Chromatinization modulates topoisomerase II processivity.

Autor: Lee J; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA., Wu M; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA.; Howard Hughes Medical Institute, Cornell University, Ithaca, NY, 14853, USA., Inman JT; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA.; Howard Hughes Medical Institute, Cornell University, Ithaca, NY, 14853, USA., Singh G; Biophysics Program, Cornell University, Ithaca, NY, 14853, USA., Park SH; Biophysics Program, Cornell University, Ithaca, NY, 14853, USA., Lee JH; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Fulbright RM; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA., Hong Y; Department of Electrical and Computer Engineering, Cornell University, Ithaca, NY, 14853, USA., Jeong J; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Berger JM; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Wang MD; Physics Department & LASSP, Cornell University, Ithaca, NY, 14853, USA. mwang@physics.cornell.edu.; Howard Hughes Medical Institute, Cornell University, Ithaca, NY, 14853, USA. mwang@physics.cornell.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 27; Vol. 14 (1), pp. 6844. Date of Electronic Publication: 2023 Oct 27.
DOI: 10.1038/s41467-023-42600-z
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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