Abstract
Background: The nucleic acid-binding protein Purα is involved at stalled DNA replication forks, in double-strand break (DSB) DNA repair and the cellular response to DNA replication stress. Purα 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 Purα. Results: Rad51 was induced in PURA-/- MEFs but was repressed when Purα was ectopically expressed in these cells. Similarly Rad51 inversely correlated with the level of Purα 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, Purα suppressed HRR DNA repair, Rad51 expression, and Rad51 foci formation. Conclusion: Tat stimulates the Rad51 promoter involving both Purα-dependent and Purα-independent mechanisms. Interaction between Purα and Tat may have opposing effects on Rad51 expression. The effects on HRR may contribute to HIV-1 associated pathogenesis.
Footnotes
- Received February 12, 2008.
- Accepted February 28, 2008.
- Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved