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- Title
Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm-deficient mice.
- Authors
Suzuki, Takeshi; Minehata, Ken-ichi; Akagi, Keiko; Jenkins, Nancy A; Copeland, Neal G
- 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.
- Publication
The EMBO journal, 2006, Vol 25, Issue 14, p3422
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601215