The DNA repair-ubiquitin-associated HR23 proteins are constituents of neuronal inclusions in specific neurodegenerative disorders without hampering DNA repair

Steven Bergink, Lies Anne Severijnen, Nils Wijgers, Kaoru Sugasawa, Humaira Yousaf, Johan M. Kros, John van Swieten, Ben A. Oostra, Jan H. Hoeijmakers, Wim Vermeulen, Rob Willemsen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

28 Citaten (Scopus)

Samenvatting

Intracellular inclusions play a profound role in many neurodegenerative diseases. Here, we report that HR23B and HR23A, proteins that are involved in both DNA repair and shuttling proteins to the 26S proteasome for degradation, accumulate in neuronal inclusions in brain from a mouse model for FXTAS, as well as in brain material from HD, SCA3, SCA7, FTDP-17 and PD patients. Interestingly, HR23B did not significantly accumulate in tau-positive aggregates (neurofibrillary tangles) from AD patients while ubiquitin did. The sequestration of HR23 proteins in intracellular inclusions did not cause detectable accumulation of their stable binding partner in DNA repair, XPC. Surprisingly, no reduction in repair capacity was observed in primary human fibroblasts that overexpressed GFP-polyQ, a polypeptide that induces HR23B-positive inclusions in these transfected cells. This illustrates that impairment of the ubiquitin-proteasome system (UPS) by expanded glutamine repeats, including the sequestration of HR23B, is not affecting NER.

Originele taal-2Engels
Pagina's (van-tot)708-716
Aantal pagina's9
TijdschriftNeurobiology of Disease
Volume23
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - sep. 2006
Extern gepubliceerdJa

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