AI Article Synopsis
- CHFR is a checkpoint gene that, when inactivated in cancer, causes a delay in chromosome condensation when cells are treated with microtubule poisons.
- CHFR-expressing cells experience a temporary arrest in early prophase with distinct nuclear envelope morphology and no chromosome condensation, while specific cyclins show varied activity.
- The research suggests that CHFR delays chromosome condensation by preventing Cyclin B1 from accumulating in the nucleus, which is crucial for the condensation process.
Article Abstract
CHFR, a novel checkpoint gene inactivated in human cancer, delays chromosome condensation in cells treated with microtubule poisons. To understand the molecular mechanism for this delay, we characterized cells with inactivated CHFR and stably transfected derivatives expressing the wild-type gene. After exposure to microtubule poisons, the CHFR-expressing cells arrested transiently in early prophase with a characteristic ruffled morphology of the nuclear envelope and no signs of chromosome condensation. Several markers suggested that Cyclin A/Cdc2 had been activated, whereas Aurora-A and -B and Cyclin B1/Cdc2 were inactive. Further, Cyclin B1 was excluded from the nucleus. Ectopic expression of Cyclin B1 with a mutant nuclear export sequence induced chromosome condensation, and thus overcame the CHFR checkpoint. We conclude that the mechanism by which CHFR delays chromosome condensation involves inhibition of accumulation of Cyclin B1 in the nucleus.
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| http://dx.doi.org/10.1038/sj.onc.1208428 | DOI Listing |
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