Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A polyclonal antibody was raised against a serine protease purified from the extracellular fluid of familial Alzheimer's disease lymphoblastoid cells. Using this antibody, a cDNA library from familial Alzheimer's disease cells and two cDNA libraries from the brains of two Alzheimer's disease patients were screened independently. The familial Alzheimer's disease protein 1 (FADP1) cDNA clones isolated from these three libraries were subjected to DNA sequence analysis. The nucleotide sequence of FADP1 cDNA is highly similar to the 5' portion of the human dihydrofolate reductase (DHFR) gene, however, the sequence corresponding to exon 1 of the DHFR gene is completely disrupted and contains a 247-bp DNA insert with a sequence unique to FADP1. Moreover, FADP1 cDNA harbours a large open reading frame, including the unique insert, which has the potential to code an approximately 50-kDa protein. The deduced amino acid sequence of this protein contains 12 cysteine residues potentially involved in six disulfide bonds, a proline-rich segment and a hydrophobic segment. Northern-blot analysis with the unique insert DNA probe verified that FADP1 protein is expressed in both lymphoblastoid and brain cells derived from Alzheimer's disease patients.
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PMID:Molecular cloning of human cDNA with a sequence highly similar to that of the dihydrofolate reductase gene in brain libraries derived from Alzheimer's disease patients. 760 Nov 20

Experimental studies of complete mammalian genes and other genetic domains are impeded by the difficulty of introducing large DNA molecules into cells in culture. Previously we have shown that GST-Z2, a protein that contains three zinc fingers and a proline-rich multimerization domain from the polydactyl zinc finger protein RIP60 fused to glutathione S-transferase (GST), mediates DNA binding and looping in vitro. Atomic force microscopy showed that GST-Z2 is able to condense 130-150 kb bacterial artificial chromosomes (BACs) into protein-DNA complexes containing multiple DNA loops. Condensation of the DNA loops onto the Z2 protein-BAC DNA core complexes with cationic lipid resulted in particles that were readily transferred into multiple cell types in culture. Transfer of total genomic linear DNA containing amplified DHFR genes into DHFR(-) cells by GST-Z2 resulted in a 10-fold higher transformation rate than calcium phosphate co-precipitation. Chinese hamster ovarian cells transfected with a BAC containing the human TP53 gene locus expressed p53, showing native promoter elements are active after GST-Z2-mediated gene transfer. Because DNA condensation by GST-Z2 does not require the introduction of specific recognition sequences into the DNA substrate, condensation by the Z2 domain of RIP60 may be used in conjunction with a variety of other agents to provide a flexible and efficient non-viral platform for the delivery of large genes into mammalian cells.
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PMID:Condensation by DNA looping facilitates transfer of large DNA molecules into mammalian cells. 1132 83