Killing the Umpire: Cooperative Defects in Mitotic Checkpoint and BRCA2 Genes on the Road to Transformation

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Killing the Umpire: Cooperative Defects in Mitotic Checkpoint and BRCA2 Genes on the Road to Transformation

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dc.contributor.author McKeon, Frank D.
dc.date.accessioned 2010-10-28T20:18:21Z
dc.date.issued 1999
dc.identifier.citation McKeon, Frank. 1999. Killing the umpire: cooperative defects in mitotic checkpoint and genes on the road to transformation. Breast Cancer Research 1:8-10. en_US
dc.identifier.issn 1465-5411 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4513842
dc.description.abstract Recent findings from mouse models of BRCA2 genetic lesions have provided intriguing insights and important questions concerning modes of tumor development in familial breast and ovarian cancers. Fibroblasts from mice homozygous for the BRCA2Tr allele grow poorly and display an array of chromosomal abnormalities that are consistent with a role for BRCA2 in DNA repair. This growth defect can be overcome and cellular transformation promoted by the expression of defective, dominant negative alleles of p53 and of the mitotic checkpoint gene Bub1, both of which are known to induce chromosome instability. These findings are mirrored in the genetic lesions sustained in tumors found in the rare BRCA2Tr/Trmice that survive to adulthood, which include defects in p53 as well as the mitotic checkpoint proteins Bub1 and Mad3L. Together, these data hint that tumors in these mice evolve from an unusually intense selective pressure to remove DNA damage checkpoints, which in turn might be facilitated by chromosomal abolition of mitotic checkpoints and the consequent increase in shuffling of genetic information. How these genetic lesions co-operate to yield transformed cells and how these data relate to BRCA1 and BRCA2 defects in the human population are important questions raised by this work. en_US
dc.description.sponsorship Molecular and Cellular Biology en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi:10.1186/bcr4 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138502/pdf/ en_US
dash.license LAA
dc.subject BRCA2 en_US
dc.subject Bub1 en_US
dc.subject DNA repair en_US
dc.subject Mad3 en_US
dc.subject mitotic checkpoint en_US
dc.title Killing the Umpire: Cooperative Defects in Mitotic Checkpoint and BRCA2 Genes on the Road to Transformation en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Breast Cancer Research en_US
dash.depositing.author McKeon, Frank D.
dc.date.available 2010-10-28T20:18:21Z

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  • FAS Scholarly Articles [7176]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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