Figure 3.

Tarzan Model: proposed mechanism of indelogenesis. Replication by the normal DNA polymerase (small cluster of circles) is blocked by a large DNA adduct (black oval) on the template DNA (A). To bypass the adduct, an error-prone translesion polymerase (large cluster of circles) and a helicase (triangle) are recruited. The translesion polymerase is also blocked by the adduct but the helicase disassociates the nascent strand from the template (B), allowing the translesion polymerase to synthesize a few nucleotides from the template (C1) or the nascent strand (C2). A few additional nucleotides are synthesized, sometimes with errors (X), generating the inserted sequence of the microindel (thick line). Thus, the inserted sequence is either a sense (in the case of C1) or antisense (in the case of C2) copy, sometimes with errors, of nearby sequence. The helicase then disassociates the segment synthesized by the translesion polymerase from the template (in the case of C1) or the nascent strand (in the case of C2). With the additional length of synthesized DNA, the translesion polymerase is able to swing across the adduct and save the cell, as Tarzan would use a vine to ‘swing’ across an obstacle and save the day. This process results in the skipping of some nucleotides on the template (D, thick dashes) resulting in the microdeletion part of the microindel. Some of the skipped bases (or their complements on the nascent strand in the case of C2) may have been part of the template for the inserted sequence in which case there is overlap of the inserted and deleted sequences of the microindel. After the adduct is bypassed, the normal polymerase can proceed with replication (E).