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)

Aspartylglycosaminuria is an inherited lysosomal storage disease caused by deficiency of glycoasparaginase (EC 3.5.1.26) and occurs with higher frequency among Finns than other populations. We have purified human glycoasparaginase and determined about 90% of the amino acid sequence of its light subunit and greater than 70% of that of its heavy subunit by Edman degradation and mass spectrometry. Additional sequence data were obtained from the cloning and subsequent nucleotide analysis of a cDNA corresponding to the normal human glycoasparaginase gene. The enzyme is encoded by a single mRNA as a single polypeptide that is posttranslationally processed to generate the subunits and is glycosylated. After preparing first-strand cDNA from leukocyte and fibroblast total RNA, we used the polymerase chain reaction to amplify the glycoasparaginase cDNA of eight Finnish aspartylglycosaminuria patients. We demonstrate that the Finnish patients' mRNA sequence differed from the normal sequence by two single-base changes six nucleotides apart from one another in the heavy chain of glycoasparaginase. The first change resulted in the replacement of arginine by glutamine (R161Q), whereas the second change resulted in a cysteine to serine substitution (C163S). Both mutations resulted in novel restriction endonuclease sites and were present in all eight Finnish aspartylglycosaminuria patients originating from different pedigrees, but they were absent from Finnish and non-Finnish controls and a non-Finnish case of aspartylglycosaminuria. These results indicate molecular homogeneity in aspartylglycosaminuria alleles in the Finnish population.
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PMID:Aspartylglycosaminuria in the Finnish population: identification of two point mutations in the heavy chain of glycoasparaginase. 201 3

Endonuclease protection or "footprinting" analysis is a powerful technique for identifying the nucleotides involved in a protein-DNA interaction. DNase I is the most often employed endonucleolytic agent; however, this endonuclease does not exhibit the true nonsequence-specific cleavage desired for this type of analysis. Methidiumpropyl-EDTA (MPE) is a synthetic DNA intercalator that cleaves DNA in the presence of ferrous ion and oxygen. Cleavage by MPE exhibits no sequence specificity, a characteristic that makes this reagent better suited for protection analysis. Here we report a generally applicable technique for MPE protection (or "footprinting") analysis of specific DNA-protein complexes from a crude nuclear extract. We have used this method to identify the nucleotides of the immunoglobulin (Ig) heavy chain promoter region that are involved in complex formation with a protein that binds the octameric sequence ATGCAAAT, and we compare our results to those obtained previously using DNase I.
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PMID:Protection analysis (or "footprinting") of specific protein-DNA complexes in crude nuclear extracts using methidiumpropyl-EDTA-iron (II). 251 95

We describe here, to our knowledge for the first time, associations between polymorphisms at the genomic DNA level in the immunoglobulin gene region and renal diseases which lead to chronic renal failure. Recent studies have shown that protein polymorphisms, present in immunoglobulin (Ig) heavy chains (Gm allotypes) are associated with certain forms of renal disease and with end stage renal failure per se. To investigate this association at the DNA level we have used probes which recognize Ig heavy chain genes and this report describes results obtained with one of these, the S mu switch region probe. With the restriction endonuclease Sst 1 (or the isoschizomer; Sac I) a number of restriction fragment length polymorphisms (RFLP) can be obtained which are recognized by this probe and there is a highly significant association between certain of these and renal disease. This is the first report of Ig switch region polymorphisms being associated with disease, yet our results suggest that S mu RFLP are more closely linked to renal disease than Ig protein polymorphisms.
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PMID:Immunoglobulin heavy chain switch region restriction fragment length polymorphisms are associated with renal disease. 288 Jun 82

We have investigated T-cell antigen receptor constant beta chain genes (Tcr C beta) and immunoglobulin (Ig) heavy chain switch region genes of HLA-DR-typed patients with membranous nephropathy (MN) employing DNA restriction fragment length polymorphism (RFLP) analysis. When a Tcr C beta probe in conjunction with the restriction endonuclease Bgl II was used, a significant increase in the frequency of a 10.0; 9.2 kb heterozygous RFLP phenotype was found in MN (75.0% versus 42.1% in controls; P = 0.002). When Sst I-restricted DNA from MN patients was hybridized with a DNA probe homologous to the switch region flanking the Ig C mu heavy chain gene (S mu), there was a significant decrease in the frequency of the 2.1; 2.6 kb heterozygous RFLP phenotype in MN (24.0% versus 54.6% in controls; P = 0.004). These results suggest that Tcr beta and Ig heavy chain loci, as well as HLA antigens, may be important in the pathogenesis of MN.
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PMID:Association of membranous nephropathy with T-cell receptor constant beta chain and immunoglobulin heavy chain switch region polymorphisms. 289 May 76

We have investigated the switch regions of Ig heavy chain genes of patients with IgA glomerulonephritis (IgA-GN) using restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from patients and controls was digested with the restriction endonuclease Sst I and transferred to nylon membranes using the Southern blot procedure and hybridized with a probe homologous to the switch region of the Ig C mu gene (S mu) which detects RFLPs in both S mu and the switch region of the Ig C alpha 1 gene (S alpha 1). A significant decrease in the frequency of the 2.6;2.1 kb heterozygous S mu phenotype was found in patients with IgA-GN (P = 0.003). With respect to the S alpha 1 region, there was a significant increase in the frequency of the 7.4 kb S alpha 1 phenotype (P = 0.002). In addition, a significant increase in the frequency of the 7.4 kb S alpha 1 allele was found (P = 0.0002). These results suggest that gene(s) within the Ig heavy chain loci may be important in the pathogenesis of IgA-GN.
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PMID:Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region. 289 61

The DNA's of 41 patients with various forms of renal disease and of 52 controls were investigated for restriction fragment length polymorphisms (RFLP), using a probe recognising the immunoglobulin Cmu heavy chain gene. With the restriction endonuclease Sst 1, 50 of the controls and 12 of the patients had the expected single 4.3 kilobase (kb) fragment. The remaining 29 patients and 2 controls displayed two patterns of banding, 8 patients and 1 control had a 6.8 kb band in addition to the 4.3 kb, and 21 patients and 1 control had a single band of 5.1 kb. In addition, a significant association between high creatinine levels (greater than 150 mumol/l) and abnormal bands was found (21/25 patients with high levels had abnormal bands compared with only 5/16 patients with normal levels). These results are evidence for an association between the human immunoglobulin heavy chain region and renal disease and they apparently confirm an association already reported at the protein level. However, the new RFLP bands, although reproducible and restricted to renal patients, occur in an area where few polymorphisms would be expected. Further, the association with high creatinine suggests some subtle interaction between the creatinine pathway and this area of the human chromosome.
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PMID:Immunoglobulin C mu gene restriction fragment length polymorphisms associated with chronic renal failure. 298 95

Ovarian non-Hodgkin's lymphomas (NHLs) are rare, and accurate diagnosis is frequently problematic. Previous studies have not provided either complete immunotypic or genotypic analyses. The authors report immunotyping and genotyping of three cases of ovarian NHL, including both primary and secondary types. Immunotyping disclosed all three were B-cell lymphomas composed of secretory blast stage lymphocytes showing kappa immunoglobulin (Ig) light chain clonal excess. DNA extracted from frozen tissue of each tumor was subjected to restriction endonuclease digestion and hybridized to probes for Ig genes, C kappa, C lambda, JH, and the T-cell receptor beta-chain gene. Rearrangements of the heavy chain and light chain Ig genes were observed in all three cases, confirming the monoclonal B-cell origin of the neoplastic population. No detectable rearrangements were observed in DNA extracted from three nonlymphoid ovarian tumors (dysgerminoma, granulosa cell tumor, and fibrothecoma). This study documents the potential value of immunotyping and genotypic analysis in the study of ovarian tumors.
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PMID:Immunotypic and genotypic characterization of non-Hodgkin's lymphomas of the ovary. 329 19

We report the molecular analysis of an 8;14 reciprocal chromosome translocation in a case of acute lymphocytic leukemia (L3 type). DNA from primary leukemic cells was analyzed on the basis of restriction endonuclease mapping by hybridization with various human c-myc and Ig heavy chain probes. The breakpoint of the translocation is within an approximately equal to 200-base-pair region in the first intron of the c-myc gene. The first, untranslated exon thereby remains on chromosome 8q-, whereas the whole protein-coding region is rearranged in the C alpha 1 locus on chromosome 14q+. RNA transfer blot analysis showed high levels of at least two different c-myc transcripts originated from the translocated gene. Both differ in size from the normal 2.2- and 2.4-kilobase transcripts. Both c-myc structure and expression were apparently normalized in remission phase. These studies demonstrate rearrangement and abnormal expression of c-myc in primary cells from an acute leukemia patient, thus adding to the concept of a key role for c-onc in human oncogenesis.
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PMID:Translocation and rearrangement of c-myc into immunoglobulin alpha heavy chain locus in primary cells from acute lymphocytic leukemia. 608 8

We have characterized a class of DNA rearrangements in plasmacytomas. These recombination events involve a DNA sequence whose origin is outside of the locus of the heavy chain constant region genes, CH. Therefore, we choose to refer to this sequence as non-immunoglobulin-associated rearranging DNA (NIARD). We have isolated two abortively rearranged C alpha genes, generated by NIARD events from the alpha-producing J558 myeloma. Restriction endonuclease maps of these sequences reveal two possible recombination sites in NIARD that are separated by approximately 6.5 kilobase pairs of DNA (defined as 5' and 3' sites). A NIARD rearrangement occurs in 15 out of 20 plasmacytomas tested, including gamma 3-, gamma 1-, gamma 2b-, gamma 2a-, and alpha-producers, but this event usually does not involve a CH switch (S) region. In fact, only S alpha appears to accept NIARD. However, NIARD did not undergo a rearrangement in eight IgA-producing hybridomas tested. One germ-line copy of NIARD (a 22-kilobase pair EcoRI fragment) is retained in all plasmacytomas. NIARD does not appear to possess repetitive DNA sequences homologous to S mu or S alpha. We discuss the possible role and implications of NIARD-like sequence rearrangements in allelic exclusion and chromosomal translocation events in plasmacytomas.
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PMID:Non-immunoglobulin-associated DNA rearrangements in mouse plasmacytomas. 628 71

Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.
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PMID:Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia. 632 25


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