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Topic Name: Genomic instability and cancer
Category: Genetic Engineering
Research persons: Department of Biomedical Sciences College of Veterinary Medicine
Location: College of Veterinary Medicine - Ithaca, New York 14853-6401, United States
Details
Genomic instability is a striking feature of many cancers. This instability drives the accumulation of mutations that underlies tumorigenesis, but whether it is absolutely necessary or sufficient for tumor development are controversial issues among cancer biologists. Two faculty members in the Department of Biomedical Sciences, John Schimenti and Bob Weiss, use mouse models to investigate the origins and physiological consequences of genomic instability.
A recent report from the Schimenti group identifies a powerful causative role for chromosomal instability in mammary tumor development, while a new study from the Weiss lab sheds light on the molecular mechanisms employed by cells to protect genomic integrity. Featured here are images from these publications, illustrating how genomes can go bad.
Figure 1 shows chromosomal instability in cells with reduced Hus1 expression following treatment with the replication inhibitor aphidicolin. The thin arrow highlights a chromatid break and the thick arrows highlight chromatid exchanges. It is adapted from Levitt, et al., Molecular and Cellular Biology, in press.
Figure 2 shows fluorescence in situ hybridization analysis of common fragile site Fra8E1 in cells following conditional Hus1 inactivation. The left panel shows the expected signal from two pairs of sister chromatids (arrows), while the right panel shows one pair of intact sister chromatids (arrows) and one pair where
a spontaneous chromosomal break has occurred at this fragile site (arrowheads). It is adapted from Zhu and Weiss, Molecular Biology of the Cell, in press.
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