Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B

Hum Mol Genet. 2000 Jul 22;9(12):1795-803. doi: 10.1093/hmg/9.12.1795.


Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The mutant ataxin-3 forms intranuclear inclusions in cultured cells as well as in diseased human brain and also causes cell death in transfected cells. However, the normal function of ataxin-3 remains unknown. To explore the function of ataxin-3, we used the two-hybrid system to screen for the protein(s) that interacts with ataxin-3. We found that ataxin-3 interacts with two human homologs of the yeast DNA repair protein RAD23, HHR23A and HHR23B. Furthermore, we confirmed that ataxin-3 interacts with the -ubiquitin-like domain at the N-terminus of the HHR23 proteins, which is important for nucleotide excision repair; however, ataxin-3 does not interact with -ubiquitin, implying that ataxin-3 might be functionally associated with the HHR23 proteins through this specific interaction. The normal and mutant ataxin-3 proteins show no difference in their ability to bind to the HHR23 proteins. However, in 293 cells HHR23A is recruited to intranuclear inclusions formed by the mutant ataxin-3 through its interaction with ataxin-3. These results suggest that this interaction is associated with the normal function of ataxin-3 and that some functional abnormality of the HHR23 proteins might exist in MJD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-3
  • Binding Sites
  • Cell Line
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Machado-Joseph Disease*
  • Mutagenesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins
  • Precipitin Tests
  • Repressor Proteins
  • Two-Hybrid System Techniques
  • Ubiquitins / metabolism


  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RAD23B protein, human
  • Repressor Proteins
  • Ubiquitins
  • RAD23A protein, human
  • ATXN3 protein, human
  • Ataxin-3
  • DNA Repair Enzymes