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Updated: Jul 23, 2025

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UBA80 and UBA52 fine-tune RNF168-dependent histone ubiquitination and DNA repair

Seong-Ok Lee1, Jessica L Kelliher2, Wan Song3

  • 1Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; Department of Radiation Oncology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

The Journal of Biological Chemistry
|July 14, 2023
PubMed

Insights

Ubiquitin-ribosomal fusion proteins UBA80 and UBA52 regulate DNA repair. They interact with histones and RNF168, inhibiting key steps in the DNA damage response and fine-tuning protein recruitment to damage sites.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The ubiquitin signaling pathway is vital for DNA damage response.
  • RNF168 is a key regulator of DNA repair proteins at damaged chromatin.
  • The precise regulation of RNF168 within cells remains incompletely understood.

Purpose of the Study:

  • To identify novel interacting partners of RNF168 and H2A/H2AX histones.
  • To elucidate the mechanism by which RNF168 activity is regulated.
  • To understand the role of ubiquitin-ribosomal fusion proteins in DNA repair.

Main Methods:

  • Co-immunoprecipitation assays to identify interacting proteins.
  • Laser-induced micro-irradiation to create DNA damage sites.
  • Western blotting and immunofluorescence to assess protein recruitment and ubiquitination.

Main Results:

  • UBA80 (RPS27A) and UBA52 (RPL40) were identified as interacting proteins for H2A/H2AX histones and RNF168.
  • UBA80 and UBA52 are recruited to DNA damage sites and are essential for DNA repair.
  • Ectopic expression of UBA80/UBA52 inhibits RNF168-mediated ubiquitination and impairs 53BP1 recruitment.

Conclusions:

  • UBA80 and UBA52 antagonize the ubiquitin signaling pathway in DNA repair.
  • The ribosomal fragments S27A and L40 limit RNF168-nucleosome engagement.
  • These proteins fine-tune the spatiotemporal regulation of DNA repair proteins at DNA damage sites.
Keywords:
53BP1DNA damageacidic patchnucleosomeribosomal proteins

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