Protamine-Controlled Reversible DNA Packaging: A Molecular Glue

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.

Automated summary

The process of packaging the paternal genome into tiny sperm nuclei during spermatogenesis involves a high level of DNA compaction, mainly mediated by protamine, but the exact mechanism remains unclear. Research has shown that DNA condensates formation can be reversibly controlled by adjusting the protamine-to-DNA ratio, providing valuable insights for understanding early and intermediate stages of spermatogenesis. This reversible microscopic mechanism induced by protamination modulation could also potentially improve the efficiency of recent vaccines using protamine for virus infections and cancers.