Journal Article

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

Guang-hui Wang, Noriko Sawai, Svetlana Kotliarova, Ichiro Kanazawa and Nobuyuki Nukina

in Human Molecular Genetics

Volume 9, issue 12, pages 1795-1803
Published in print July 2000 | ISSN: 0964-6906
Published online July 2000 | e-ISSN: 1460-2083 | DOI:
Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B

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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.

Journal Article.  6294 words.  Illustrated.

Subjects: Genetics and Genomics

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