Figure 6. Pif1 rescues stalling at both G4s and iMs.

• A, B
  Pulse‐chase experiments carried out with the indicated templates. Reactions were initiated with radiolabelled dATP. After a 10 min pulse, either wildtype or ATPase‐dead K264A (mut) Pif1 was added with the chase and samples taken after another 10 min.
• C
  Model illustrating the effects of G4s and iMs on replication. CMG unwinds past a leading strand quadruplex‐forming sequence and secondary structures form from the exposed ssDNA. These structures inhibit synthesis by polymerase ε, leading to helicase‐polymerase uncoupling. Pif1 can unwind both G4s and iMs and allow synthesis to resume. iMs can be resolved in this manner or lead to nascent DNA breakage in the absence or presence of a repriming event. Lagging strand products may remain intact.

Source data are available online for this figure.