Prions Partner With DNA

Prion proteins, famous for causing transmissible spongiform encephalopathies such as mad cow and Creutzfeldt-Jakob diseases, have long posed a mystery to scientists. In their infectious, misfolded form, they seem to replicate and spread disease without the participation of genetic material (see page 24). Scientists think that when infectious prions encounter typical prions, they convert them to infectious forms that continue spreading. The misfolded prions then start clumping together into aggregates, killing nerve cells. Now researchers have for the first time identified prion interactions with DNA that lead to prion aggregation and cell toxicity (Biochemistry, DOI: 10.1021/bi300440e). Yraima Cordeiro and Jerson L. Silva of the Federal University of Rio de Janeiro and their colleagues had previously found that nucleotides can bind to prions. When the group mixed normal mouse prions with two short, double-stranded DNA sequences that they call D44 and D67, the resulting prion-DNA complexes aggregated into clumps. The uncomplexed prions did not aggregate. The longer sequence, with 21 base pairs, caused larger aggregates. Both types of prion-DNA aggregates killed neuroblastoma cells, the researchers found.