Stress-induced acidification may contribute to formation of unusual structures in C9orf72-repeats.

•The C-rich strand of the C9orf72 repeat undergoes a pH-induced transition at ~pH 7.•C9orf72 repeats form i-motifs at pH < 5, hairpins and quadruplexes higher pH.•Human replication protein A binds to the G-rich and C-rich DNA strands at pH < 7.•i-motif structures can form at pH values found in some cells in vivo.•DNA conformational plasticity exists over broad range of solution conditions.