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

We have probed the structure of nucleosomes within the 31-kilobase pair long, transcriptionally active gene for dihydrofolate reductase (DHFR) in mouse cells which contain multiple copies of the DHFR gene. We found that the distribution of electrophoretically variant nucleosomes within the DHFR gene is highly nonuniform: variant DHFR nucleosomes are abundant within and in the immediate vicinity of the approximately 200-base pair (bp) long first DHFR exon, and decrease by at least 10-fold within two nucleosomes upstream and downstream from this region. The nonuniformly distributed variant DHFR mononucleosomes are of two electrophoretically distinguishable discrete types. One corresponds to a mononucleosome containing a approximately 180-bp DNA fragment and possibly also histone H1 and high mobility group proteins. The other type of variant DHFR mononucleosome contains a approximately 146-bp DNA fragment, and its changes in relative content within the DHFR gene closely parallel those of the 180-bp variant mononucleosome. Several lines of evidence are consistent with the interpretation that the electrophoretically variant approximately 146-bp (core) mononucleosome species corresponds to diubiquitinated DHFR nucleosomes. We discuss possible causal relationships between the observed nonuniform distribution of variant nucleosomes within the DHFR gene and the DHFR gene transcription.
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PMID:Preferential localization of variant nucleosomes near the 5'-end of the mouse dihydrofolate reductase gene. 298 65

We investigated histone-DNA interactions in chromatin of amplified about 1000 fold dihydrofolate reductase (DHFR) domain in methotrexate resistant Chinese hamster ovary cell line CHOC 400. We explored chromatin structure of DHFR-gene and extended region lying 3'-downstream of the DHFR-gene, which includes two zones of DNA replication initiation, Ori-beta and Ori-gamma, and matrix attachment region (MAR). Using the method of hybridization with "protein images" we found that the yield of both core histones and histone H1 cross-linked with DNA in 5'-region of the DHFR-gene, in Ori-gamma and regions flanked from either side MAR is significantly decreased in comparison with 3'-transcribed region of the DHFR-gene, Ori-beta and MAR. It was shown previously that decreased yield of histones cross-linked with DNA is typical for 5'-region of actively transcribed genes. So, histone-DNA interactions in chromatin of the 5'-region of the house-keeping and moderately transcribed DHFR-gene, Ori-gamma and regions which flank MAR resemble those in 5'-regions of actively transcribed genes. Significant differences in amount of histones cross-linked with DNA in various parts of the DHFR-domain testify to high level of heterogeneity of chromatin structure in the domain.
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PMID:[Heterogeneity of the structural organization of the chromatin domain including the dihydrofolate reductase gene in Chinese hamster ovary cell culture]. 747 50

The hallmark of cellular aging is the failure of senescent diploid cells to enter or to complete the S phase of the cell cycle. The cause for such failure may hold the key for our understanding of the molecular basis of cellular aging. We have previously shown that aging of IMR-90 human diploid fibroblasts in culture is accompanied by a five to sevenfold decrease in both thymidine kinase activity and thymidine kinase mRNA level (Chang and Chen, 1988, J. Biol. Chem., 263:11431-11435). To examine whether attenuation of gene expression at G1/S boundary is unique for thymidine kinase or it may involve most, if not all, of other G1/S genes, we compared the expressions of two classes of G1/S genes in young and in old IMR-90 cells following serum stimulation. We found that the expression of all these genes, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), ribonucleotide reductase (PNR), proliferating cell nuclear antigen (PCNA), histone H1, histone H2A + 2B, histone H3, and histone H4, was induced to high levels in young IMR-90 cells but not in old IMR-90 cells. The mRNA levels of all G1/S genes in young cells were more than tenfold higher than that in old cells 12 hr after serum stimulation. The enzymes encoded by TS and DHFR genes and dUTPase also exhibited similar age-dependent attenuation in activities. In contrast, expression of growth-related genes such as eIF-5A, c-Ha-ras, and beta-actin did not show significant differences between young and old cells after serum stimulation. Computer analysis of the promoter region of these G1/S genes revealed an Sp-1 binding site as the most common cis-element. Taken together, our results suggest that the suppression of G1/S gene expressions during senescence may be a global phenomenon and that G1/S genes may be coordinately controlled.
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PMID:Global change of gene expression at late G1/S boundary may occur in human IMR-90 diploid fibroblasts during senescence. 807 91

mRNA levels of several Crithidia fasciculata genes involved in DNA metabolism have previously been found to cycle as cells progress through the cell cycle. Octamer consensus sequences in the 5' untranslated regions (5' UTRs) of these transcripts were shown to be required for cycling of these mRNAs. The KAP3 gene encodes a kinetoplast histone H1-like DNA binding protein, and its mRNA levels cycle in parallel with those of the kinetoplast DNA topoisomerase (TOP2), dihydrofolate reductase-thymidylate synthase (DHFR-TS), and the large subunit of the nuclear single-stranded DNA binding protein (RPA1). KAP3 mRNA contains two octamer consensus sequences in its 3' UTR but none in its 5' UTR. Mutation of these octamer sequences was not sufficient to prevent cycling of a sequence-tagged KAP3 mRNA expressed from a plasmid. Mutation of an octamer sequence contained on the precursor transcript but not on the mRNA, in addition to mutation of the two octamer sequences in the 3' UTR, was necessary to abolish cycling of the mRNA. The requirement for a sequence not present on the mature mRNA indicates that regulation of the mRNA levels by the octamer sequences occurs at or prior to splicing of the transcript. Incompletely processed RNAs containing octamer sequences were also found to accumulate during the cell cycle when the mRNA levels were lowest. These RNA species hybridize to both the KAP3 coding sequence and that of the downstream drug resistance gene, indicating a lack of processing within the intergenic region separating these genes. We propose a cell cycle-dependent interference in transcript processing mediated by octamer consensus sequences as a mechanism contributing to the cycling of such transcripts.
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PMID:Sequence elements in both the intergenic space and the 3' untranslated region of the Crithidia fasciculata KAP3 gene are required for cell cycle regulation of KAP3 mRNA. 1291 86