Logarinho et al., "Mutations in the essential spindle checkpoint gene Bub1 cause chromosome missegregation and fail to block apoptosis in Drosophila," Journal of Cell Biology, vol.
Polyzos et al., "Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice," Proceedings of the National Academy of Sciences of the United States of America, vol.
Meraldi, "Bub1 regulates chromosome segregation in a kinetochore-independent manner," Journal of Cell Biology, vol.
Kuniyasu et al., "Expression of Bub1 gene correlates with tumor proliferating activity in human gastric carcinomas," Pathobiology, vol.
The researchers found that if a mother's egg cell has a mutation in just one copy of Bub1 gene, then she is less likely to have offspring that survive to birth.
"Where you would normally expect a female to have eight to 10 pups, there were only one or two pups that survived to term in the litters of females that had one copy of Bub1. So this was unusual when we were looking for cancer effects, especially in this group of females," said Venkatachalam.
Bub1 plays a role in a checkpoint that ensures that chromosomes are properly divided during meiosis, the cell division process that enables a stem cell to become an egg.
This checkpoint halts when Bub1 is mutated, sometimes producing an egg with an extra chromosome or an egg with a missing chromosome.
The investigators do not have direct proof that mutations in the human BUB1 lead to aneuploidy, although they do have evidence that the mutant gene enables human cells to proceed with aspects of cell division after being treated with drugs that disrupt spindle assembly.
The researchers have found a second human gene related to BUB1, and they are examining whether it -- or human versions of the other yeast genes that cause chromosomal instability -- is mutated in cancers.
The genes decreased included plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), putative mitotic checkpoint kinase (BUB1), and a gene of unknown function (GenBank accession no.
Similar gene expression alterations in response to malathion exposure were found in all cell strains for nine genes: a) aldo-keto reductase 1 (AKR1C1), b)aldo-keto reductase 2 (AKR1C2), c) an estrogen-responsive gene (EBBIP), d) plasminogen activator (PLAT), e) centromere protein F (CPF), f) replication factor C (RFC3), g) thymidylate synthetase (TYMS), h) putative mitotic checkpoint kinase (BUB1), and i) a gene of unknown function (AI859865).