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EMBO J. 2006 Jul 26;25(14):3422-31. Epub 2006 Jul 6.

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

Author information

  • 1Cancer Genetic Unit, Horizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, Japan. suzukit@hmro.med.kyoto-u.ac.jp

Abstract

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.

PMID:
16858412
[PubMed - indexed for MEDLINE]
PMCID:
PMC1523184
Free PMC Article

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