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SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities.
- Source :
-
DNA repair [DNA Repair (Amst)] 2013 May 01; Vol. 12 (5), pp. 356-66. Date of Electronic Publication: 2013 Mar 18. - Publication Year :
- 2013
-
Abstract
- Smc5-6 is a highly conserved protein complex related to cohesin and condensin involved in the structural maintenance of chromosomes. In yeasts the Smc5-6 complex is essential for proliferation and is involved in DNA repair and homologous recombination. siRNA depletion of genes involved in the Smc5-6 complex in cultured mammalian cells results in sensitivity to some DNA damaging agents. In order to gain further insight into its role in mammals we have generated mice mutated in the Smc6 gene. A complete knockout resulted in early embryonic lethality, demonstrating that this gene is essential in mammals. However, mutation of the highly conserved serine-994 to alanine in the ATP hydrolysis motif in the SMC6 C-terminal domain, resulted in mice with a surprisingly mild phenotype. With the neo gene selection marker in the intron following the mutation, resulting in reduced expression of the SMC6 gene, the mice were reduced in size, but fertile and had normal lifespans. When the neo gene was removed, the mice had normal size, but detailed phenotypic analysis revealed minor abnormalities in glucose tolerance, haematopoiesis, nociception and global gene expression patterns. Embryonic fibroblasts derived from the ser994 mutant mice were not sensitive to killing by a range of DNA damaging agents, but they were sensitive to the induction of sister chromatid exchanges induced by ultraviolet light or mitomycin C. They also accumulated more oxidative damage than wild-type cells.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Adenosine Triphosphatases chemistry
Adenosine Triphosphatases metabolism
Adenosine Triphosphate metabolism
Amino Acid Motifs
Animals
Catalytic Domain
Cell Cycle Proteins chemistry
Cell Cycle Proteins metabolism
Cells, Cultured
Fertility genetics
Fibroblasts drug effects
Fibroblasts radiation effects
Genes, Essential
Glucose Intolerance genetics
Hematopoiesis genetics
Hydrolysis
Introns
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitomycin pharmacology
Nociception
Sister Chromatid Exchange drug effects
Sister Chromatid Exchange radiation effects
Ultraviolet Rays
Adenosine Triphosphatases genetics
Cell Cycle Proteins genetics
Mutation, Missense
Phenotype
Subjects
Details
- Language :
- English
- ISSN :
- 1568-7856
- Volume :
- 12
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- DNA repair
- Publication Type :
- Academic Journal
- Accession number :
- 23518413
- Full Text :
- https://doi.org/10.1016/j.dnarep.2013.02.006