Protamine-Controlled Reversible DNA Packaging: A Molecular Glue

Mukherjee, A and De Izarra, A and Degrouard, J and Olive, E and Maiti, PK and Jang, YH and Lansac, Y (2021) Protamine-Controlled Reversible DNA Packaging: A Molecular Glue. In: ACS Nano .

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Abstract

Packaging paternal genome into tiny sperm nuclei during spermatogenesis requires 106-fold compaction of DNA, corresponding to a 10-20 times higher compaction than in somatic cells. While such a high level of compaction involves protamine, a small arginine-rich basic protein, the precise mechanism at play is still unclear. Effective pair potential calculations and large-scale molecular dynamics simulations using a simple idealized model incorporating solely electrostatic and steric interactions clearly demonstrate a reversible control on DNA condensates formation by varying the protamine-to-DNA ratio. Microscopic states and condensate structures occurring in semidilute solutions of short DNA fragments are in good agreement with experimental phase diagram and cryoTEM observations. The reversible microscopic mechanisms induced by protamination modulation should provide valuable information to improve a mechanistic understanding of early and intermediate stages of spermatogenesis where an interplay between condensation and liquid-liquid phase separation triggered by protamine expression and post-translational regulation might occur. Moreover, recent vaccines to prevent virus infections and cancers using protamine as a packaging and depackaging agent might be fine-tuned for improved efficiency using a protamination control. © 2021 American Chemical Society.

Item Type:	Journal Article
Publication:	ACS Nano
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society
Keywords:	Amino acids; Compaction; DNA; Molecular dynamics; Phase separation; Viruses, Effective pair potentials; Large-scale molecular dynamics; Liquid-liquid phase separation; Microscopic mechanisms; Reversible control; Semidilute solutions; Steric interactions; Translational regulation, Bioinformatics
Department/Centre:	Division of Physical & Mathematical Sciences > Physics
Date Deposited:	03 Dec 2021 07:04
Last Modified:	03 Dec 2021 07:04
URI:	http://eprints.iisc.ac.in/id/eprint/70119

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