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Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm-deficient mice.
- Source :
- EMBO Journal; 7/26/2006, Vol. 25 Issue 14, p3422-3431, 10p, 1 Chart, 5 Graphs
- Publication Year :
- 2006
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- ONCOGENES
TUMOR suppressor genes
GENETIC mutation
TUMORS
LABORATORY mice
MUTAGENESIS
Subjects
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 25
- Issue :
- 14
- Database :
- Complementary Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 21702028
- Full Text :
- https://doi.org/10.1038/sj.emboj.7601215