A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1

Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.     

Expression of early developmental genes in vole <Emphasis Type="Italic">Microtus rossiaemeridionalis</Emphasis>

The expression of genes Sox2, Klf4, Myc, Sall4, Gata6, Foxa2, Hnf4a, Cdx2, Esrrb, Hand1 in cell lines, embryos and organs of adult voles Microtus rossiaemeridionalis was studied. High resemblance of the expression patterns of these genes in the organs of adult voles, mice and humans was demonstrated. It was established that genes Gata6, Foxa2 and Hnf4a were specifically expressed in vole extraembryonic endoderm cells, while Cdx2 and Hand1 genes, in trophoblast stem cells. This shows that these genes can be used as markers of corresponding vole cell lines. Indirect confirmation pointing to the fact that Oct4 gene is a marker gene for epiblast cells both in the vole and mouse was obtained.     

Mapping of silver fox genes: chromosomal localization of the genes for GOT2, AK1, ALDOC, ACP1, ITPA, PGP, and BLVR.

Evidence is presented for the chromosome localization of seven silver fox genes by the use of a panel of fox x Chinese hamster somatic cell hybrids. AK1, GOT2, and ALDOC are assigned to chromosome VFU2, PGP to chromosome VFU38, BLVR to chromosome VFU5, ACP1 to chromosome VFU8, and ITPA to chromosome VFU14. The genetic map of 29 fox genes is compared with those reported for man and other mammals. The results we obtained support and extend our previous suggestion that the formation of the Canidae branch of the Carnivora phylogenic tree was associated with a great increase in the rate of reorganization of the ancestral karyotype.     

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>studies

Background  

Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.     

Symmetric cyanine dyes for detecting nucleic acids

A novel approach to the design of sensitive fluorescent probes for nucleic acids detection is proposed. Suitable modifications of tri- and pentamethine cyanine dyes in the polymethine chain and/or in the heterocyclic residues can result in a significant decrease in unbound dye fluorescence intensity and an increase in dye emission intensity in the presence of DNA compared to the unsubstituted dye. The sharp enhancement in the fluorescence intensity upon dye interaction with double-stranded DNA permits the application of the modified tri- and pentamethine dyes as fluorescent probes in double-stranded DNA detection in homogeneous assays.