Figure 3.

One-step versus two-step TLS. (A) The tracts of DNA synthesized during one-step bypass of a T-T CPD. Pol_Rep, the replicative polymerases Pol δ and Pol ε. In the case illustrated, bypass of a CPD, the inserter and extender polymerase (Pol_TLSins/ext) is Pol η, which can replicate this lesion on its own, aided by its large active site pocket and molecular split (see text). The extent of its synthesis patch is limited either by its dissociation from the DNA induced by a steric clash between the lesion and the little-finger domain as the chain elongates or by the primer at the end of a single-stranded gap. (B) The tracts of DNA synthesized during two-step bypass of a T-T (6-4) photoproduct. Like many lesions, the highly distorting (6-4) photoproduct is not bypassed in a single step. Instead, an inserter polymerase (Pol_TLSins) incorporates a base opposite the 3′T of the lesion, but cannot extend opposite the 5′T. Instead, this is carried out by an extender polymerase (Pol_TLSext), most commonly Pol ζ, which can deal with the highly misaligned terminus.