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A Conserved Mechanism for Hormesis in Molecular Systems.

Sharon N Greenwood1, Regina G Belz2, Brian P Weiser1

  • 1Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA.

Dose-Response : a Publication of International Hormesis Society
|August 8, 2022
PubMed
Summary

Hormesis, a low-dose beneficial effect, is explained by a molecular mechanism involving protein homo-multimers. This conserved mechanism, observed in proliferating cell nuclear antigen (PCNA), may clarify biological responses to compounds.

Keywords:
BRAFPCNAUNG2hormesisuracil DNA glycosylase

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Hormesis describes biological responses where low doses have opposite effects compared to high doses.
  • The molecular basis for many observed hormetic effects remains unidentified.
  • Understanding hormesis is crucial for interpreting cellular and organismal responses to various compounds.

Purpose of the Study:

  • To elucidate a conserved molecular mechanism underlying hormesis.
  • To explain how low-dose treatments can enhance biological responses.
  • To identify the role of protein homo-multimers in hormetic dose-response relationships.

Main Methods:

  • Characterized a molecular mechanism of hormesis using binding experiments.
  • Analyzed the interaction of homotrimeric proliferating cell nuclear antigen (PCNA) with uracil DNA glycosylase (UNG2) and a peptide.
  • Investigated conserved features in dimeric BRAF and octameric glutamine synthetase 2 (GS2).

Main Results:

  • Described a conserved molecular mechanism for hormesis.
  • Demonstrated that protein homo-multimers can exhibit hormesis by simultaneous substrate and competitor binding.
  • Observed that this mechanism is conserved in enzymes like BRAF and GS2, which are stimulated by low inhibitor doses.

Conclusions:

  • A conserved molecular mechanism explains hormesis through protein homo-multimer interactions.
  • This mechanism involves simultaneous binding of substrates and competitors on different subunits.
  • Identifying these molecular determinants aids in understanding biological responses to exogenous compounds.