Practice question

Even highly selective polymerases occasionally incorporate non-complementary nucleotides at rates near 10^-5 during rapid synthesis. Immediate correction relies heavily on intrinsic 3' to 5' exonuclease proofreading activity located in separate domain. When misincorporation distorts primer-template duplex geometry, polymerase stalls and transfers frayed 3' end from polymerase active site to exonuclease site that hydrolyzes phosphodiester bond and excises incorrect base. Strand then repositions into polymerase site for continued accurate synthesis. This kinetic proofreading step improves fidelity about 100-fold reducing errors to 10^-7 before mismatch repair.