New research has identified a mechanism in the DNA mismatch repair pathway that stops the abnormal trinucleotide repeat expansion and the progression of Huntington’s disease. Scientists at the University College of London (UCL) and the University of Cambridge show FAN1, a genetic modifier of Huntington’s disease stabilizes CAG repeats by binding MLH1 to restrict its binding to MSH3, thus inhibiting the assembly of a functional mismatch repair complex. This pivotal role of FAN1 highlights a potential avenue for HD therapeutics since mimicking or enhancing FAN1 mediated blocking of mismatch repair would alter the course of the disease.
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