Model for the mechanism of formation of hcDNA. The central poly(CA) and poly(TG) sequences of the DNA fragment are represented in blue and red, the terminal non-repetitive sequences are in green. After denaturation, reassociation of the strands of the DNA fragment can occur either without a shift, thus reforming the initial fragment in its regular linear conformation, or with a shift, resulting in an intermediate in which the CA and TG strands are only paired on part of their length, leaving a stretch of single-stranded poly(CA) on one side and an equal and complementary length of single-stranded poly(TG) on the other side (arrows), plus the single-stranded non-repetitive sequences at both ends (A). In the presence of HMGB1, this intermediate can fold and form a loop when one of the single-stranded repetitive sequences inserts in the fork formed by the two single strands at the opposite end and pairs with the complementary single-stranded repetitive sequence (B). The hemicatenane thus formed is then stabilized after reassociation of the non-repetitive regions at both ends of the fragment (C) and rearrangement of the structure to maximize base pairing (D).