Studies which look for genome wide-associated risk factors (GWAS) have a shown a link between Huntington’s disease and DNA repair proteins as well as other DNA related proteins including splicing and transcription factors. Huntingtin was previously described as a DNA binding protein but I have not found studies using purified huntingtin protein and DNA samples in vitro, in the published literature.
I did some preliminary work with the purified huntingtin samples I have generated in the lab and some large DNA molecules called plasmids. This showed the possibility of DNA binding but this experiment did not represent physiological conditions in the cell. Subsequent experiments seems to show that huntingtin does bind DNA in these in vitro assays.
Proving that this is a disease or cell relevant interaction will be difficult but this is interesting none-the-less (well I think so!). As DNA is very negatively charged molecule, it could be that huntingtin binds with a non-specific positive patch on the molecule, this type of false positive is fairly common with in vitro reaction conditions so I am treading cautiously for now….
More to follow soon I hope!
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