Effects of HsRad51 overexpression on cell proliferation, cell cycle progression, and apoptosis

Expression of the DNA repair and recombination protein human Rad51 (HsRad51 ) is increased in transformed cells and in cancer cell lines. In order to s tudy the effects of acute HsRad51 ectopic overexpression on cell proliferat ion, cell cycle progression, and apoptosis, we generated clones of the huma n fibrosarcoma cell line HT1080 carrying a HsRad51 transgene under a repres sible promoter. The HsRad51-overexpressing cells showed decreased plating e fficiency and growth rate in a dose-dependent manner with regard to the deg ree of overexpression. An accumulation of HsRad51-overexpressing cells in G (2) was observed following release of cells after synchronization with doub le thymidine block. Moreover, the fraction of apoptotic cells measured by a nnexin V-FACS increased with the time of HsRad51 overexpression. In the lig ht of these observations, sustained increased levels of HsRad51 may contrib ute to tumor progression by causing a selection for cells tolerant to the g rowth-suppressive and apoptosis-inducing effects of acute HsRad51 overexpre ssion. (C) 2001 Academic Press.