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. |