Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type I produce about half the normal amount of type I procollagen, as a result of decreased synthesis of one of its constituent chains, pro alpha 1 (I). To test the hypothesis that decreased synthesis of pro alpha (I) chains results from mutations in the COL1A1 gene, we used primer extension with nucleotide-specific chain termination to measure the contribution of individual COL1A1 alleles to the mRNA pool in fibroblasts from affected individuals. A polymorphic MnlI restriction endonuclease site in the 3'-untranslated region of COL1A1 was used to distinguish the transcripts of the two alleles in heterozygous individuals. Twenty-three individuals from 21 unrelated families were studied. In each case there was marked diminution in steady-state mRNA levels from one COL1A1 allele. Loss of an allele through deletion or rearrangement was not the cause of the diminished COL1A1 mRNA levels. Primer extension with nucleotide-specific chain termination allows identification of the mutant COL1A1 allele in cell strains that are heterozygous for an expressed polymorphism. It is applicable to sporadic cases, to small families, and to large families in whom key individuals are uninformative at the polymorphic sites used in linkage analysis, making it a useful adjunct to the biochemical screening of collagenous proteins for OI.
 ...
PMID:Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen. 135 40

Restriction endonuclease analysis was used to determine the methylation status of collagen, c-Ha-ras, and thymidine kinase genes in human fibroblasts and tumor cell lines. When digested with the methylation sensitive enzymes HpaII or HhaI, the DNA of each cell line generated a unique banding pattern for each gene examined. No generalized trend of gene hypomethylation or decreases in overall cytosine methylation were observed in tumor cell lines when compared to fibroblasts. Collagen biosynthetic profiles were also determined, and no correlations could be made between patterns of type I and type III collagen gene methylation and expression. Our findings support those of a previous report in which methylation and expression of the chick alpha 2(I) collagen gene were examined, and this represents the first such analysis of the pro-alpha 1 (III) collagen gene. MspI restriction fragment length polymorphisms were detected within c-Ha-ras, pro-alpha 2(I) collagen, pro-alpha 1(III) collagen, and thymidine kinase genes. The ras gene polymorphisms can be attributed to variation in the number of tandem repeats within a MspI fragment at the 3' end of the gene. The other gene polymorphisms may be due to base pair mutations at methylated cytosine residues within CCGG sequences.
 ...
PMID:Patterns of DNA methylation and gene expression in human tumor cell lines. 369 18

DNA fragments, prepared by partial Eco RI digestion of fetal sheep liver genomic DNA, were used to prepare a "library" of amplified genomic sequences with the lambda vector Charon 4A. Several recombinant plaques were identified by their ability to hybridize to 32P-labeled cDNA prepared from fetal sheep tendon type I procollagen mRNA. Two of these recombinant DNA bacteriophages (SpC3 and SpC7) were identified as containing procollagen pro alpha 2 gene sequences by their ability to specifically anneal to procollagen pro alpha 2 mRNA. Restriction endonuclease and hybridization to a cloned pro alpha 2 cDNA demonstrated that approximately half (2.5 kilobases) of the pro alpha 2 mRNA sequence is distributed over 15 kilobases of genomic DNA. Restriction maps of SpC3 and SpC7 demonstrated that these two DNA fragments contain overlapping sequences of the pro alpha 2 gene. Electron microscopy and R-loop analysis of SpC3 revealed that at least 12 to 16 intervening sequences are distributed throughout the length of this gene fragment.
 ...
PMID:Isolation and characterization of a 15-kilobase genomic sequence coding for part of the Pro alpha 2 chain of sheep type I collagen. 624 13

Transformation of human lung fibroblasts (WI-38) by Simian Virus 40 (SV40) resulted in a decline of 25-30% in the amount of secreted collagen. The collagen produced by the transformed fibroblasts contained no type I collagen (i.e. alpha 1(I) and alpha 2 chains), which was the major collagen component produced by untransformed fibroblasts. Measurement of the procollagen mRNA levels by dot hybridization with nick-translated procollagen-cDNA clones showed that the absence of type I collagen was due to the absence of alpha 1(I) and alpha 2 procollagen mRNAs. This result was confirmed by hybridization of cDNA to total RNA with southern blots of the procollagen clones. To clarify the mechanism by which type I procollagen gene transcription is abolished in transformed cells, the methylation patterns of the alpha 1(I) and alpha 2 procollagen genes in normal and SV40-transformed fibroblasts were compared, using the chicken alpha 1(I) and alpha 2 procollagen-cDNA clones as probes. Methylated sites were detected by means of the restriction endonuclease isoschizomers HpaII and MspI. Methylation of the procollagen alpha 1(I) and alpha 2 genes was increased in the SV40-transformed fibroblasts, concurrently with the loss of type I collagen synthesis. DNA methylation may thus contribute to altered regulation of gene expression upon cell transformation.
 ...
PMID:Loss of type I procollagen gene expression in SV40-transformed human fibroblasts is accompanied by hypermethylation of these genes. 629 57

A site that is preferentially cleaved by the single-strand-specific endonuclease from Aspergillus oryzae was located in vitro 180 base pairs upstream from the 5' end of the chicken pro-alpha 2(I) collagen gene. It is found in supercoiled plasmids with a negative superhelical density of -0.024 or more but not in linear DNA molecules. The nuclease S1 sensitivity is retained in plasmids containing genomic fragments extending from position +8 to -285 (where +1 is the first transcribed base) and from -147 to -351 and also in a 5.7-kilobase EcoRI fragment that extends 1.6 kilobases 5' and 4.1 kilobases 3' to the 5' end of the gene. Analysis at the nucleotide level on a DNA sequence gel places the site at -181 to -182 on the sense strand and at -182 to -184 and -192 to -195 on the nonsense strand. These sites lie within a stretch of 42 pyrimidines interrupted by a single guanine and within the sequence T-C-C-C-T-C-C-C-T-T-C-C-T-C-C-C-T-C-C-C-T.
 ...
PMID:Endonuclease S1-sensitive site in chicken pro-alpha 2(I) collagen 5' flanking gene region. 632 10

We examined the vitamin D receptor genotypes (BB, Bb and bb) defined by the Bsml restriction endonuclease in relation to biochemical indices of bone metabolism in healthy Caucasian infants. We measured the serum concentrations of the carboxy-terminal propeptide of type I procollagen (PICP) and the urinary excretion of total pyridinoline, free, total and bound deoxypyridinoline, the type I collagen N-terminal and C-terminal cross-linked telopeptides. The concentrations of the urinary indices are expressed relative to creatinine. Subjects with BB genotype had the highest mean concentrations of free, total and bound deoxypyridinoline and of the N-terminal cross-linked telopeptide (PANOVA = 0.0016, 0.0004, 0.0002 and 0.0053, respectively). BB boys had a higher excretion of the C-terminal cross-linked telopeptide than the other genotypes (PANOVA = 0.0253). In a subgroup of homozygotes aged 10 (1) months, BB subjects had the highest levels of the C-terminal cross-linked telopeptide (p=0.03), and of total deoxypyridinoline (p=0.02) and pyridinoline (p=0.06) concentrations. No significant association between the vitamin D receptor genotype and PICP was found. These data suggest that there may be a contribution of the vitamin D receptor genotype to skeletal metabolism in early childhood.
 ...
PMID:Bsm I polymorphism in the vitamin D receptor gene is related to bone collagen turnover in healthy infants. 1061 58