DNA polymerase 3'-5' exonuclease (3'-5' Exo)

DNA polymerase 3'-5' exonuclease is the proofreading functional domain found in replicative DNA polymerases, such as DNA polymerase delta and epsilon, which ensures high-fidelity DNA replication by removing mispaired nucleotides from the 3' end of the nascent DNA strand (Mini et al., 2006). This enzymatic activity is the specific site of action for the chemotherapeutic agent gemcitabine through a process known as masked chain termination. Once gemcitabine triphosphate is incorporated into the DNA, one additional natural nucleotide is added to the chain, which sterically hinders the 3'-5' exonuclease from recognizing and excising the drug (Plunkett et al., 1995). This inhibition of the proofreading mechanism prevents the repair of the DNA strand, leading to irreversible termination of DNA synthesis and the induction of apoptosis (Huang & Plunkett, 1995). Consequently, this target is central to the pharmacological efficacy of gemcitabine in treating various solid tumors, including pancreatic, bladder, and non-small cell lung cancers (Noble & Goa, 1997).

Other names

Proofreading exonucleaseDNA polymerase proofreading domain3' to 5' proofreading activityDNA polymerase epsilon exonucleaseDNA polymerase delta exonuclease

Masked chain termination