Reverse transcriptase-dependent pyrophosphorolysis

Reverse transcriptase-dependent pyrophosphorolysis is a biochemical reaction catalyzed by reverse transcriptases (RTs), in which the enzyme removes nucleotides from the 3′ end of a DNA or RNA primer in the presence of inorganic pyrophosphate (PPi). This process is essentially the reverse of nucleotide polymerization: instead of adding nucleotides to a growing chain, RT uses PPi to cleave off terminal nucleotides, generating deoxynucleoside triphosphates (dNTPs) as products. In retroviruses like HIV, this activity enables excision of chain terminators introduced by certain antiretroviral drugs, contributing to drug resistance. Efficient pyrophosphorolysis typically occurs when there are more than 14 base pairs in the primer-template region.

Removal of terminal nucleotide(s) via attack on phosphodiester bond using PPi