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Nucleosomal embedding reshapes the dynamics of abasic sites

  • Bignon, Emmanuelle1, 2
  • Claerbout, Victor E. P.1
  • Jiang, Tao1
  • Morell, Christophe2
  • Gillet, Natacha1
  • Dumont, Elise1, 3
  • 1 Univ. Lyon, ENS de Lyon, CNRS UMR 5182, Université Claude Bernard Lyon 1, Laboratoire de Chimie, Lyon, F69342, France , Lyon (France)
  • 2 Institut des Sciences Analytiques, UMR 5280, Université de Lyon 1 (UCBL) CNRS, Lyon, France , Lyon (France)
  • 3 Institut Universitaire de France, 5 rue Descartes, Paris, 75005, France , Paris (France)
Published Article
Scientific Reports
Springer Nature
Publication Date
Oct 14, 2020
DOI: 10.1038/s41598-020-73997-y
Springer Nature


Apurinic/apyrimidinic (AP) sites are the most common DNA lesions, which benefit from a most efficient repair by the base excision pathway. The impact of losing a nucleobase on the conformation and dynamics of B-DNA is well characterized. Yet AP sites seem to present an entirely different chemistry in nucleosomal DNA, with lifetimes reduced up to 100-fold, and the much increased formation of covalent DNA-protein cross-links leading to strand breaks, refractory to repair. We report microsecond range, all-atom molecular dynamics simulations that capture the conformational dynamics of AP sites and their tetrahydrofuran analogs at two symmetrical positions within a nucleosome core particle, starting from a recent crystal structure. Different behaviours between the deoxyribo-based and tetrahydrofuran-type abasic sites are evidenced. The two solvent-exposed lesion sites present contrasted extrahelicities, revealing the crucial role of the position of a defect around the histone core. Our all-atom simulations also identify and quantify the frequency of several spontaneous, non-covalent interactions between AP and positively-charged residues from the histones H2A and H2B tails that prefigure DNA-protein cross-links. Such an in silico mapping of DNA-protein cross-links gives important insights for further experimental studies involving mutagenesis and truncation of histone tails to unravel mechanisms of DPCs formation.

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