DNA Research: HIV-1 Tat depresses DNA-PK(CS) expression and DNA repair

AIDSWEEKLY Plus; Monday, August 28, 2006
Staff Medical Writers

According to recent research from the People's Republic of China, "There is accumulating evidence that cancer patients with human immmunodeficiency virus-1/acquired immunodeficency syndrome (HIV-1/AIDS) have more severe tissue reactions and often develop cutaneous toxic effects when subjected to radiotherapy.

"Here we explored the effects of the HIV-1 Tat protein on cellular responses to ionizing radiation. Two Tat-expressing cell lines, TT2 and TE671-Tat, were derived from human rhabdomyosarcoma cells by transfecting with the HIV-1 tat gene."

"Radiosensitivity was determined using colony-forming ability. Gene expression was assessed by cDNA microarray and immunohybridization. The Comet assay and gamma-H2AX foci were use to detect DNA double-strand breaks (DSBs) and repair. Radiation-induced cell cycle changes were detected by flow cytometry," scientists said.

"The radiosensitivity of TT2 and TE671-Tat cells was significantly increased as compared with parental TE671 cells or the control TE671-pCI cells. Tat also increased proliferation activity. The comet assay and gamma H2AX foci detection revealed a decreased capacity to repair radiation-induced DNA DSBs in Tat-expressing cells.

"Microarray assay demonstrated that the DNA repair gene DNA-PKcs, and cell cycle-related genes Cdc20, Cdc25C, KIF2C and CTS1 were downregulated in Tat-expressing cells. Depression of DNA-PKcs in Tat-expressing cells was further confirmed by RT-PCR and immunohybridization analysis," reported Y. Sun and colleagues at the Beijing Institute of Radiation Medicine.

"Tat-expressing cells exhibited a prolonged S phase arrest after 4 Gy gamma-irradiation, and a noticeable delay in the initiation and elimination of radiation-induced G(2)/M arrest as compared with parental cells.

"In addition," continued the authors, "the G2/M arrest was incomplete in TT2 cells. Moreover, HIV-1 Tat resulted in a constitutive overexpression of cyclin 131 protein."

Researchers concluded, "HIV-1 Tat protein sensitizes cells to ionizing radiation via depressing DNA repair and dysregulating cell cycle checkpoints. These observations provide new insight into the increased tissue reactions of AIDS cancer patients to radiotherapy."

Sun and colleagues published their study in International Journal of Radiation Oncology Biology Physics (HIV-1 Tat depresses DNA-PK(CS) expression and DNA repair, and sensitizes cells to ionizing radiation. Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):842-50).

For additional information, contact P.K. Zhou, Beijing Institute of Radiation Medicine, Dept. of Radiation Toxicology & Oncology, 27 Taiping Rd., Beijing 100850, People's Republic of China.

Publisher contact information for the International Journal of Radiation Oncology Biology Physics is: Elsevier Science Inc., 360 Park Avenue South, New York, NY 10010-1710, USA.

Keywords: Beijing, People's Republic of China, HIV/AIDS, HIV-1 Tat Protein, Radiotherapy, DNA Repair DNA-PK-CS).

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Sun Y, Huang YC, Xu QZ, et al., “HIV-1 Tat depresses DNA-PK(CS) expression and DNA repair, and sensitizes cells to ionizing radiation”, Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):842-50.

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