A REITERATIVE MODE OF DNA-SYNTHESIS ADOPTED BY HIV-1 REVERSE-TRANSCRIPTASE AFTER A MISINCORPORATION

Amplification of oligonucleotide repeats is a major cause of variabili ty and instability of genomes, This phenomenon is probably due to an a berration in the copying process of polymerases. We show here that in the presence of MnCl2, mismatch formation commits HIV-1 reverse transc riptase to a new mode of DNA synthesis which generates repetitive prod ucts. This activity is distinct from terminal transferase since it req uires specific DNA motifs in the template. This mechanisn, which is pr ocessive, also works on homologous RNA templates where it generates re iterative products more than 150 nucleotides long. The corresponding m echanism, which involves extensive primer misalignment, is strikingly similar to that postulated for telomerases.