Cancer Institute A national cancer institute
designated cancer center

Teresa Wang

Publication Details

  • Replication-compromised cells require the mitotic checkpoint to prevent tetraploidization CHROMOSOMA Zhang, Z., Arora, S., Zhou, y., Cherry, A., Wang, T. S. 2011; 120 (1): 73-82


    Replication stress often induces chromosome instability. In this study, we explore which factors in replication-compromised cells promote abnormal chromosome ploidy. We expressed mutant forms of either polymerase ? (Pol?) or polymerase ? (Pol?) in normal human fibroblasts to compromise DNA replication. Cells expressing the mutant Pol?-protein failed to sustain mitotic arrest and, when propagated progressively, down-regulated Mad2 and BubR1 and accumulated 4N-DNA from the 2N-DNA cells. Significantly, a population of these cells became tetraploids. The Pol? mutant expressing cells also exhibited elevated cellular senescence markers, suggesting as a mechanism to limit proliferation of the tetraploids. Expression of the Pol? mutant also caused cells to accumulate 4N-DNA. In contrast to the Pol? mutant expressing cells, the Pol? mutant expressing cells expressed sufficient levels of Mad2, BubR1, and cyclin B1 to sustain mitotic arrest, and these cells had normal chromosome ploidy. Together, these results suggest that replication-compromised cells depend on the mitotic checkpoint to prevent mitotic slippage that could result in tetraploidization.

    View details for DOI 10.1007/s00412-010-0292-7

    View details for Web of Science ID 000286628800006

    View details for PubMedID 20827484

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