Disruption of centromere function by 2-aminopurine
- Institut de Biologie Structurale, Grenoble (France)
- Univ. of Washington, Seattle, WA (United States)
The protein kinase inhibitor 2-aminopurine (2-AP) interferes with the normal progression of mitosis and with chromosome segregation in BHK cells. Cells exit mitosis without displaying chromosome alignment and movements characteristic of metaphase and anaphase. Instead, chromatin is displayed laterally by the spindle. As determined by confocal immunofluorescence microscopy, centromeres frequently detach from the remainder of the chromatin and associate with the mitotic spindle. Centromere function is clearly altered by 2-AP. We have found that 2-AP induces cells arrested with nocodazole or taxol to exit mitosis without metaphase or anaphase events. It appears, therefore, that 2-AP inhibits a kinase involved in normal mitotic progression and thereby induces mitotic exit in the absence of metaphase or subsequent stages of mitosis. Additionally, 2-AP overrides drug-induced cell cycle checkpoints at G{sub 1},S and G{sub 2} phases of the cell cycle. In keeping with observations that 2-AP causes escape from multiple checkpoint signals, we have determined that 2-AP advances cells to mitosis with partially replicated DNA. The resulting cells are highly aneuploid. Partial replication of DNA may offer a mechanism for centromere separation from chromatin. Since centromeres apparently remain integral, and can interact with the spindle following dissociation from the remainder of the chromosome, it is evident that the centromere can function as an independent organelle. Independent evidence for the self-contained organelle structure of the centromere is given by the retention of an integral centromere element when interphase mammalian nuclei are lysed and their chromatin spread.
- OSTI ID:
- 28453
- Report Number(s):
- CONF-9210475-Cond.; CNN: Grant NIH GM2022; TRN: 95:001845-0027
- Resource Relation:
- Conference: NATO advanced research workshop, Crete (Greece), 10-15 Oct 1992; Other Information: PBD: 1993; Related Information: Is Part Of Chromosome segregation and aneuploidy; Vig, B.K. [ed.] [University of Nevada, Reno, NV (United States). Dept. of Biology]; PB: 429 p.
- Country of Publication:
- United States
- Language:
- English
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