p53-independent apoptosis and p53-dependent block of DNA rereplication following mitotic spindle inhibition in human cells

M Casenghi, R Mangiacasale, M Tuynder… - Experimental cell …, 1999 - Elsevier
M Casenghi, R Mangiacasale, M Tuynder, P Caillet-Fauquet, A Elhajouji, P Lavia
Experimental cell research, 1999Elsevier
We have studied the response of human transformed cells to mitotic spindle inhibition. Two
paired cell lines, K562 and its parvovirus-resistant KS derivative clone, respectively
nonexpressing and expressing p53, were continuously exposed to nocodazole. Apoptotic
cells were observed in both lines, indicating that mitotic spindle impairment induced p53-
independent apoptosis. After a transient mitotic delay, both cell lines exited mitosis, as
revealed by flow-cytometric determination of MPM2 antigen and cyclin B1 expression …
We have studied the response of human transformed cells to mitotic spindle inhibition. Two paired cell lines, K562 and its parvovirus-resistant KS derivative clone, respectively nonexpressing and expressing p53, were continuously exposed to nocodazole. Apoptotic cells were observed in both lines, indicating that mitotic spindle impairment induced p53-independent apoptosis. After a transient mitotic delay, both cell lines exited mitosis, as revealed by flow-cytometric determination of MPM2 antigen and cyclin B1 expression, coupled to cytogenetic analysis of sister centromere separation. Both cell lines exited mitosis without chromatid segregation. K562 p53-deficient cells further resumed DNA synthesis, giving rise to cells with a DNA content above 4C, and reentered a polyploid cycle. In contrast, KS cells underwent a subsequent G1 arrest in the tetraploid state. Thus, G1 arrest in tetraploid cells requires p53 function in the rereplication checkpoint which prevents the G1/S transition following aberrant mitosis; in contrast, p53 expression is dispensable for triggering the apoptotic response in the absence of mitotic spindle.
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