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Poly(ADP-Ribosyl) Code Functions.

N V Maluchenko1, D O Koshkina1, A V Feofanov1,2

  • 1Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234 Russia.

Acta Naturae
|August 11, 2021
PubMed
Summary

Poly(ADP-ribosyl)ation, a key cellular process, uses distinct poly(ADP-ribose) (PAR) structures to regulate cellular functions and responses. Dysregulation of PAR metabolism is linked to diseases, suggesting therapeutic potential.

Keywords:
NAD+PAR codePARGPARPphase separationpoly-ADP-ribose

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Poly(ADP-ribosyl)ation (PAR) is crucial for cellular metabolism, impacting DNA repair, gene expression, and stress responses.
  • PAR molecules, through covalent and non-covalent interactions, modulate diverse cellular activities, including inflammation and immune responses.

Purpose of the Study:

  • To review the multifaceted roles of poly(ADP-ribose) (PAR) in cellular processes.
  • To explore the concept of the "PAR code" and its implications in biological regulation.
  • To discuss the link between PAR metabolism and various diseases, and its therapeutic potential.

Main Methods:

  • Literature review of studies on poly(ADP-ribosyl)ation.
  • Analysis of the structural diversity and functional implications of PAR molecules.
  • Examination of the regulatory network of PAR metabolism (writers, readers, erasers).

Main Results:

  • Structurally distinct PAR molecules act as a "PAR code," differentially regulating cellular processes.
  • PAR polymers can form functional biomolecular clusters via phase separation, enabling spatial organization and component recruitment.
  • Impaired PAR metabolism is implicated in oncological, cardiovascular, and neurodegenerative diseases.

Conclusions:

  • The "PAR code" provides a sophisticated mechanism for cellular regulation.
  • Phase separation of PAR polymers is a key mechanism for organizing cellular functions.
  • Modulating PAR levels offers a promising therapeutic strategy for treating major diseases.