Poly(ADP-ribose) (PAR) exhibits ion-dependent structural properties distinct from RNA

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Poly(ADP-ribose) (PAR) is a nucleic-acid-like polymer vital for DNA repair and chromatin remodeling.
• PAR's role in biomolecular phase separation is significant but mechanistically unclear due to its complex structure.
• Limited experimental data exists on PAR's conformational dynamics and ion interactions.

Purpose of the Study:

• To develop a coarse-grained model for Poly(ADP-ribose) (PAR).
• To compare PAR's conformational ensemble and ion atmosphere with RNA using molecular dynamics simulations.
• To elucidate the molecular mechanisms behind PAR's role in phase separation and protein organization.

Main Methods:

• Development of a five-bead coarse-grained model for PAR.
• Conducting molecular dynamics simulations.
• Analyzing conformational ensembles and ion atmospheres in various ionic conditions.

Main Results:

• PAR exhibits a stronger structural transition than RNA in response to divalent ions.
• Preferential ion binding and ion-mediated bridging drive PAR's conformational changes.
• PAR forms a compact, ion-rich atmosphere distinct from RNA, facilitating phase separation.

Conclusions:

• A physically grounded model for PAR dynamics has been established.
• Key molecular differences between PAR and RNA in ion environments were identified.
• Mechanistic insights into PAR's role in phase separation and protein interactions at DNA damage sites were provided.