DNA polymerase switch is an activity whereby a polymerase is replaced by the other polymerase. There are 5 distinct DNA polymerases in the E. coli cell: Pol I, Pol II, Pol III, Pol IV, Pol V, each has different roles in genomic maintenance and evolution. Among these 5 polymerases, DNA Pol III Holoenzyme (Pol III HE) is a primary enzyme for DNA replication that can synthesize new strand with very high processivity (more than 50 kb per binding event) and high speed (about 1kb per second).

However, Pol III HE is unable to overcome some lesions whereby the others can. When encountering a lesion, Pol III probably will stall at the lesion site on the leading strand, resulting in uncoupling of leading and lagging strand synthesis, and arrest of the replication fork. One of the pathways used in cell to solve this problem is translesion synthesis (TLS), whereby a switch will occur from the stalled Pol III to a specialized polymerase (Pol II, Pol IV or Pol V, depends on the situation). After taking over the primer-template junction from the stalled Pol III, the TLS polymerase will synthesize to overcome the lesion. After that, Pol III will return to the primer end to continue its processive synthesis.