دورية أكاديمية
FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington's disease
| العنوان: | FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington's disease |
|---|---|
| المؤلفون: | Goold, R, Hamilton, J, Menneteau, T, Flower, M, Bunting, EL, Aldous, SG, Porro, A, Vicente, JR, Allen, ND, Wilkinson, H, Bates, GP, Sartori, AA, Thalassinos, K, Balmus, G, Tabrizi, SJ |
| المصدر: | Cell Reports , 36 (9) , Article 109649. (2021) |
| بيانات النشر: | CELL PRESS |
| سنة النشر: | 2021 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Huntington’s disease, repeat expansion, GWASCAG instability, DNA repair, mismatch repair, FAN1, MLH1, MSH3, FAN1 nuclease activity |
| الوصف: | CAG repeat expansion in the HTT gene drives Huntington’s disease (HD) pathogenesis and is modulated by DNA damage repair pathways. In this context, the interaction between FAN1, a DNA-structure-specific nuclease, and MLH1, member of the DNA mismatch repair pathway (MMR), is not defined. Here, we identify a highly conserved SPYF motif at the N terminus of FAN1 that binds to MLH1. Our data support a model where FAN1 has two distinct functions to stabilize CAG repeats. On one hand, it binds MLH1 to restrict its recruitment by MSH3, thus inhibiting the assembly of a functional MMR complex that would otherwise promote CAG repeat expansion. On the other hand, it promotes accurate repair via its nuclease activity. These data highlight a potential avenue for HD therapeutics in attenuating somatic expansion. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10134226/1/1-s2.0-S2211124721010925-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10134226Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10134226/1/1-s2.0-S2211124721010925-main.pdfTest https://discovery.ucl.ac.uk/id/eprint/10134226Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.85929A50 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |