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Publication : Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm-deficient mice.

First Author  Suzuki T Year  2006
Journal  EMBO J Volume  25
Issue  14 Pages  3422-31
PubMed ID  16858412 Mgi Jnum  J:111171
Mgi Id  MGI:3653154 Doi  10.1038/sj.emboj.7601215
Citation  Suzuki T, et al. (2006) Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm-deficient mice. EMBO J 25(14):3422-31
abstractText  Retroviral insertional mutagenesis preferentially identifies oncogenes rather than tumor suppressor (TS) genes, presumably because a single retroviral-induced mutation is sufficient to activate an oncogene and initiate a tumor, whereas two mutations are needed to inactivate a TS gene. Here we show that TS genes can be identified by insertional mutagenesis when the screens are performed in Blm-deficient backgrounds. Blm-deficient mice, like Bloom syndrome patients, have increased frequencies of mitotic recombination owing to a mutation in the RecQ protein-like-3 helicase gene. This increased mitotic recombination increases the likelihood that an insertional mutation in one allele of a TS gene will become homozygoused by non-sister chromatid exchange and the homozygosity of the insertion provides a marker for identifying the TS gene. We also show that known as well as novel TS genes can be identified by insertional mutagenesis in Blm-deficient mice and identify two JmjC family proteins that contribute to genome stability in species as evolutionarily diverse as mammals and Caenorhabditis elegans.
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