Three Prime Repair Exonuclease 1 preferentially degrades the integration-incompetent HIV-1 DNA through favorable kinetics, thermodynamic, structural and conformational properties.

ABSTRACT: HIV-1 integration into the human genome is dependent on 3'-processing of the reverse transcribed viral DNA. Recently, we reported that the cellular Three Prime Repair Exonuclease 1 (TREX1) enhances HIV-1 integration by degrading the unprocessed viral DNA, while the integration-competent 3'-processed DNA remained resistant. Here, we describe the mechanism by which the 3'-processed HIV-1 DNA resists TREX1-mediated degradation. Our kinetic studies revealed that the rate of cleavage (k_cat) of the 3'-processed DNA was significantly lower than the unprocessed HIV-1 DNA by TREX1. The efficiency of degradation (k_cat/K_M) of the 3'-processed DNA was also significantly lower than the unprocessed DNA. Furthermore, the binding affinity (K_d) of T

SUBMITTER: Prakash P 

PROVIDER: S-EPMC10983988 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature