Fig. 4

Models explaining both the deletion and insertion mutagenesis utilizing the lagging strand of the replication fork.(A) Two models for imperfect inverted repeat deletion. The nucleotides written 3′ to 5′ with the stem-loop structure are the template strand for DNA synthesis. The top nucleotides written 5′ to 3′ represent the replicated DNA. The polymerase pauses at the extruded cruciform. The hairpin stem adjacent to the polymerase melts and the polymerase complex and the copied strand dissociate and slip forward to reanneal, resulting in a deletion frameshift. The abridged events on the bottom illustrate the same sort of mechanism for the other large deletion slipping on the single T. (B) As in A, the bottom nucleotides are the template strand and the top nucleotides represent the newly synthesized strand. The polymerase pauses at the junction with the stem-loop structure, allowing for the duplex to melt and reanneal using a single guanine base pair. Polymerization then continues and either successfully negotiates the cruciform the second time or, as seen in Figure 3C, may undergo further mutagenesis.