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PMID:9521327

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Citation

Cahill, DP, Lengauer, C, Yu, J, Riggins, GJ, Willson, JK, Markowitz, SD, Kinzler, KW and Vogelstein, B (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392:300-3

Abstract

Genetic instability was one of the first characteristics to be postulated to underlie neoplasia. Such genetic instability occurs in two different forms. In a small fraction of colorectal and some other cancers, defective repair of mismatched bases results in an increased mutation rate at the nucleotide level and consequent widespread microsatellite instability. In most colorectal cancers, and probably in many other cancer types, a chromosomal instability (CIN) leading to an abnormal chromosome number (aneuploidy) is observed. The physiological and molecular bases of this pervasive abnormality are unknown. Here we show that CIN is consistently associated with the loss of function of a mitotic checkpoint. Moreover, in some cancers displaying CIN the loss of this checkpoint was associated with the mutational inactivation of a human homologue of the yeast BUB1 gene; BUB1 controls mitotic checkpoints and chromosome segregation in yeast. The normal mitotic checkpoints of cells displaying microsatellite instability become defective upon transfer of mutant hBUB1 alleles from either of two CIN cancers.

Links

PubMed Online version:10.1038/32688

Keywords

Amino Acid Sequence; Aneuploidy; Antineoplastic Agents/pharmacology; Cell Cycle; Cloning, Molecular; Colorectal Neoplasms/genetics; Demecolcine/pharmacology; Humans; Mitosis/genetics; Mitotic Index; Molecular Sequence Data; Mutation; Neoplasms/genetics; Nocodazole/pharmacology; Protein Kinases/genetics; Protein-Serine-Threonine Kinases; Transfection; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BUB1

involved_in

GO:0007093: mitotic cell cycle checkpoint signaling

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BUB1

involved_in

GO:0007093: mitotic cell cycle checkpoint

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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