Inactivation of p33(ING1) tumor suppressor affects the function of the cell cycle "checkpoints" and stability of the genome

Novel candidate tumor suppressor p33(ING1) is known to regulate activity of the p53 protein. The effect of p33(ING1) inactivation on the functioning o f the cell cycle "checkpoints" and the frequency of chromosomal aberrations was examined. Transduction of the p33-GSEas genetic suppressor element, kn own to reduce the p53 activity, into p53-positive rat and human cells resul ted in: (1) partial abolishment of ethylmetansulphonate- or colcemid-induce d arrest of the G1-to-S transition in the G0-synchronized cultures; (2) abo lishment of the block in the S phase by the DNA synthesis inhibitor, N-phos phonacetil-L-aspartate (PALA); (3) an increase in the number of spontaneous chromosomal breaks and sister-chromatid exchanges; (4) increased frequency of colchicine-induced polyploidy. Similar effects were observed upon trans duction of the p53-GSE22 genetic suppressor element, known to reduce p53 tr anscriptional activity. Presumably, the effect of p33(ING1) inactivation on the cell cycle checkpoints and genetic stability is associated with a decr ease in p53 activity.