Figure 8.

Proposed EXPEDITE model for tandem substitutions causing juxtalocation of adjacent residues during DNA replication. (I) Cytosine (C) is deaminated to uracil (U) in a polypyrimidine context (shown here as an example since this context typically contains the most tandem substitutions, refer to ). (II) UNG pinches the U into an extruded configuration and (III) U is cleaved, leaving an AP site (*). (IV) If during DNA replication the resulting extruded AP site is tolerated, the juxtaposed base acts transiently as a substitute template. (V) After decontraction of the template strand, the AP site is reverted to a normal configuration and replication continues from the ‘mismatch’ position containing the AP site. (VI) Hereafter, the AP site, as well as the mismatch, is removed by canonical base excision repair. (see Discussion). (VII) Final repair synthesis and ligation.