Role of Puralpha in the modulation of homologous recombination-directed DNA repair by HIV-1 Tat.

Background: The nucleic acid-binding protein Puralpha is involved at stalled DNA replication forks, in double-strand break (DSB) DNA repair and the cellular response to DNA replication stress. Puralpha interacts with HIV-1 Tat, which regulates homologous recombination-directed DNA repair (HRR).

Materials And Methods: We investigated Rad51 and HRR regulation in mouse embryo fibroblasts (MEFs) from PURA -/- knockout mice that lack Puralpha.

Results: Rad51 was induced in PURA -/- MEFs but was repressed when Puralpha was ectopically expressed in these cells. Similarly Rad51 inversely correlated with the level of Puralpha in normal postnatal mouse brain. HIV-1 Tat stimulated HRR DNA repair of I-SceI induced DNA DSBs and the nuclear appearance of Rad51 foci. In contrast, Puralpha suppressed HRR DNA repair, Rad51 expression, and Rad51 foci formation.

Conclusion: Tat stimulates the Rad51 promoter involving both Puralpha-dependent and Puralpha-independent mechanisms. Interaction between Puralpha and Tat may have opposing effects on Rad51 expression. The effects on HRR may contribute to HIV-1 associated pathogenesis.