Figure 6.

Mechanistic models of repetitive unwinding, and replication fork regression. (A) In solution, both dimeric and tetrameric forms of WRN coexist. Dimeric WRN preferentially binds to the forked DNA, and unwinds it with one protomer translocating on the 3′-overhang strand and the other anchoring on the 5′-overhang strand. As the unwinding progresses, mechanical stress accumulates, and rewinding abruptly occurs via the sliding back mechanism once a threshold is passed. (B) Tetrameric WRN preferentially binds to a stalled replication fork, and is converted into a dimer for the activation of the replication fork regression. During branch migration, the two protomers of the dimeric WRN translocate on either the parental lagging strand or the daughter leading strand.