DNA Packaging and Polycation Length Determine DNA Susceptibility to Free Radical Damage in Condensed DNA

Ehigbai Oikeh, Jesse Ziebarth, Md Abu Monsur Dinar, Daniel Kirchhoff, Anastasiia Aronova, Thomas D. Dziubla, Yongmei Wang, Jason E. DeRouchey

Research output: Contribution to journalArticlepeer-review


In nature, DNA exists primarily in a highly compacted form. The compaction of DNA in vivo is mediated by cationic proteins: histones in somatic nuclei and protamines in sperm chromatin. The extreme, nearly crystalline packaging of DNA by protamines in spermatozoa is thought to be essential for both efficient genetic delivery as well as DNA protection against damage by mutagens and oxidative species. The protective role of protamines is required in sperm, as they are sensitive to ROS damage due to the progressive loss of DNA repair mechanisms during maturation. The degree to which DNA packaging directly relates to DNA protection in the condensed state, however, is poorly understood. Here, we utilized different polycation condensing agents to achieve varying DNA packaging densities and quantify DNA damage by free radical oxidation within the condensates. Although we see that tighter DNA packaging generally leads to better protection, the length of the polycation also plays a significant role. Molecular dynamics simulations suggest that longer polyarginine chains offer increased protection by occupying more space on the DNA surface and forming more stable interactions. Taken together, our results suggest a complex interplay among polycation properties, DNA packaging density, and DNA protection against free radical damage within condensed states.

Original languageEnglish
Pages (from-to)3329-3339
Number of pages11
JournalJournal of Physical Chemistry B
Issue number14
StatePublished - Apr 11 2024

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society.

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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