Publications by authors named "Weihan Huai"
Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) are the two most prevalent polyglutamine (polyQ) neurodegenerative diseases, caused by CAG (encoding glutamine) repeat expansion in the coding region of the huntingtin (HTT) and ataxin-3 (ATXN3) proteins, respectively. We have earlier reported that the activity, but not the protein level, of an essential DNA repair enzyme, polynucleotide kinase 3'-phosphatase (PNKP), is severely abrogated in both HD and SCA3 resulting in accumulation of double-strand breaks in patients' brain genome. While investigating the mechanistic basis for the loss of PNKP activity and accumulation of DNA double-strand breaks leading to neuronal death, we observed that PNKP interacts with the nuclear isoform of 6-phosphofructo-2-kinase fructose-2,6-bisphosphatase 3 (PFKFB3).
View Article and Find Full Text PDFHuntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) are the two most prevalent polyglutamine (polyQ) neurodegenerative diseases, caused by CAG (encoding glutamine) repeat expansion in the coding region of the huntingtin (HTT) and ataxin-3 (ATXN3) proteins, respectively. We have earlier reported that the activity, but not the protein level, of an essential DNA repair enzyme, polynucleotide kinase 3'-phosphatase (PNKP), is severely abrogated in both HD and SCA3 resulting in accumulation of double-strand breaks in patients' brain genome. While investigating the mechanistic basis for the loss of PNKP activity and accumulation of DNA double-strand breaks leading to neuronal death, we observed that PNKP interacts with the nuclear isoform of 6-phosphofructo-2-kinase fructose-2,6-bisphosphatase 3 (PFKFB3).
View Article and Find Full Text PDFDeficiency in classical nonhomologous end-joining-mediated repair of transcribed genes is linked to SCA3 pathogenesis.
Proc Natl Acad Sci U S A
April 2020
Article Synopsis
- Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease linked to mutations in the Ataxin-3 gene, specifically a CAG repeat expansion, affecting normal cell function.
- The study demonstrates that depleted ATXN3 significantly impairs RNA polymerase II activity and the repair of DNA breaks, indicating that ATXN3 is crucial for efficient transcription and DNA repair mechanisms.
- SCA3 patients and model organisms show reduced polynucleotide kinase 3'-phosphatase (PNKP) activity and more DNA damage, suggesting that enhancing PNKP activity could be a viable therapeutic approach for managing SCA3 symptoms.