Integration, chromosomal

DNA-binding mechanism that does not involve DNA damage or disruption of chromosomal integrity [86]. 

Chromosomal Integration Occurs With Some Viruses... 

DNA Chromosome Integrity Is Monitored Throughout the Cell Cycle... 

In each of these studies dozens of transgenic animals were made and characterized. This is necessary because there is considerable individual variability in phenotype, presumably because of different sized transgene concatemers and different chromosomal integration sites. In some foun-... 

A number of alternative approaches are being developed that may overcome some of these issues. Replication-defective retroviral vectors are available that will more consistently (a) deliver a chosen gene into cells and (b) ensure chromosomal integration of the gene. A second innovation is the application of nuclear transfer technology. 

The theoretical complications posed by random chromosomal integration became a medical reality in 2002, when two children who had received retroviral-based gene therapy 2 years previously developed a leukaemic-like condition. The initial clinical trial aimed to treat X-linked severe combined immunodeficiency (SCID-X1), a hereditary disorder in which T-lymphocytes and NK cells in particular do not develop, due to a mutation in the gene coding for the yc cytokine receptor subunit. The clinical consequence is near abolition of a functional immune system. 

Shen WH, Balajee AS, Wang J et al (2007) Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128 157-170... 

Merrihew RV, Clay WC, Condreay JP, Witherspoon SM, Dallas WS, Kost TA (2001), Chromosomal integration of transduced recombinant baculovirus DNA in mammalian cells, J. Virol. 75 903-909. 

Wang, J. J., Rojanatavorn, K., and Shih, J. C. H. 2004. Increased production of Bacillus keratinase by chromosomal integration of multiple copies of the her A gene. Biotech. Bioeng., 87,459-464. 

Lopes M, Foiani M, Sogo JM. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol. Cell 2006 21(1) 15-27. 

Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, Yamaguchi-Iwai Y, Shinohara A, Takeda S. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J. 1998 17 5497-5508. 

Genetic elements of viruses are ubiquitously used in genetic engineering to achieve supranatural expression in organisms. For viral vectors, the production system involves the use of a functional virus. The expression levels achieved by these systems are typically several percent of soluble protein—consistently higher than achieved by chromosomal integration (Table 2). 

---