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dc.contributor.authorMcKeon, Frank D.
dc.date.accessioned2010-10-28T20:18:21Z
dc.date.issued1999
dc.identifier.citationMcKeon, 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.issn1465-5411en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4513842
dc.description.abstractRecent 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.sponsorshipMolecular and Cellular Biologyen_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/bcr4en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC138502/pdf/en_US
dash.licenseLAA
dc.subjectBRCA2en_US
dc.subjectBub1en_US
dc.subjectDNA repairen_US
dc.subjectMad3en_US
dc.subjectmitotic checkpointen_US
dc.titleKilling the Umpire: Cooperative Defects in Mitotic Checkpoint and BRCA2 Genes on the Road to Transformationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBreast Cancer Researchen_US
dash.depositing.authorMcKeon, Frank D.
dc.date.available2010-10-28T20:18:21Z
dc.identifier.doi10.1186/bcr4*
dash.contributor.affiliatedMcKeon, Frank


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