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

As demonstrated by long-range mapping of restriction endonuclease recognition sequences and genomic cloning, we found that the human genes encoding interleukin 3 (IL 3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are tandemly arrayed on the long arm of chromosome 5, separated by 9 kilobases (kb) of DNA. This close physical linkage of genes with similar structure and biologic function suggests that these cytokines may have evolved from a common ancestral gene. This linkage in evolution of two relatively divergent genes further implies that some of the other lymphokine and cytokine genes that appear to share as much or more sequence similarity than do IL 3 and GM-CSF may be distantly related members of a cytokine gene family.
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PMID:The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5. 283 32

Lactoferrin is a major constituent of polymorphonuclear leukocyte granules and is present in mature neutrophils but not in blasts or promyelocytes. We have isolated a cDNA probe for lactoferrin and used it to study the synthesis of lactoferrin mRNA by normal and leukemic granulocyte precursors. The probe pHL-41 has been subcloned in phage m13 and characterized by restriction endonuclease analysis and nucleic acid sequencing. pHL-41 contains approximately 40% of the coding sequence of the lactoferrin gene. The 3' untranslated region includes a stop codon and a possible polyadenylation signal. There is a greater than 98% agreement between the cDNA-deduced amino acid sequence and that determined by analysis of the protein. Myeloid cells from normal bone marrow and circulating leukocytes from patients with chronic granulocytic leukemia contain lactoferrin mRNA transcripts that are indistinguishable in size and relative quantity. The human promyelocytic leukemia cell line HL-60 contains no lactoferrin mRNA. Induction of monocytic or granulocytic differentiation fails to induce the synthesis of detectable lactoferrin message. Similarly, studies with the human myeloblastic leukemia cell line PLB-985 reveal the inability of these cells to produce lactoferrin mRNA even under conditions that bring about morphologically demonstrable granulocytic differentiation. These data suggest that granulocytic differentiation in the leukemic cell lines is incomplete or defective. The presence of lactoferrin may play a role in the orderly expression of the genetic program leading to the development of the normal mature granulocyte.
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PMID:Isolation of lactoferrin cDNA from a human myeloid library and expression of mRNA during normal and leukemic myelopoiesis. 347

An RNA-based method has been developed to genotype donors for the granulocyte-specific alloantigens NA1 and NA2. mRNA was isolated from granulocytes, reversely transcribed into cDNA and amplified using an Fc-gamma-receptor III-1 sequence-specific primer in the polymerase chain reaction (PCR). PCR products were analysed by restriction fragment length polymorphism (RFLP) using the restriction endonuclease Taq I, which provided a distinct restriction fragment pattern corresponding to the NA alleles. 17 donors were typed by PCR-RFLP and the results were in close accordance with those obtained by serological phenotyping by granulocyte immunofluorescence and the antigen capture assay MAIGA.
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PMID:Typing of the granulocyte-specific NA antigens by restriction fragment length polymorphism analysis. 794 95

Polymorphic structures of the neutrophil Fc gamma receptor IIIb (Fc gamma RIIIb) result in alloantibody formation that causes alloimmune neonatal neutropenia and transfusion reactions. Alloantigens located on Fc gamma RIIIb include the antigens NA1 and NA2. In four cases of alloimmune neonatal neutropenia, granulocyte-specific alloantibodies directed against a thus far unknown antigen were detected by granulocyte agglutination and immunofluorescence tests in the maternal sera. By the use of the monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA) assay, the new antigen, termed SH, was located on the Fc gamma RIIIb. Nucleotide sequence analysis of the Fc gamma RIIIb coding region from a SH(+) individual showed a single-base C-->A mutation at position 266, which results in an Ala78Asp amino acid substitution. A family study confirmed that this nucleotide difference is inherited, and corresponds to the SH phenotype. Serologic typing of 309 randomly selected individuals showed an antigen frequency of 5% in the white population. The same frequency was found by genotyping, for which a technique based on polymerase chain reaction (PCR) using sequence-specific primers (PCR-SSP) was developed. Typing of all SH(+) individuals for NA1 and NA2, and PCR-restriction fragment length polymorphism analysis of the NA-specific PCR products from five SH(+) individuals using the SH-specific endonuclease SfaN 1 showed that SH antigen is very probably the result of an additional mutational event in the NA2 form of the Fc gamma RIIIB gene. Immunochemical studies also demonstrated that the SH determinants reside on the 65- to 80-kD NA2 isoform of the Fc gamma RIIIb. Our findings show the existence of an additional polymorphism of the Fc gamma RIIIb, which can result in alloantibody formation causing alloimmune neonatal neutropenia.
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PMID:Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma receptor IIIb. 902 35

Homologous recombination (HR) is essential for accurate genome duplication and maintenance of genome stability. In eukaryotes, chromosomal double strand breaks (DSBs) are central to HR during specialized developmental programs of meiosis and antigen receptor gene rearrangements, and form at unusual DNA structures and stalled replication forks. DSBs also result from exposure to ionizing radiation, reactive oxygen species, some anti-cancer agents, or inhibitors of topoisomerase II. Literature predicts that repair of such breaks normally will occur by non-homologous end-joining (in G1), intrachromosomal HR (all phases), or sister chromatid HR (in S/G(2)). However, no in vivo model is in place to directly determine the potential for DSB repair in somatic cells of mammals to occur by HR between repeated sequences on heterologs (i.e., interchromosomal HR). To test this, we developed a mouse model with three transgenes-two nonfunctional green fluorescent protein (GFP) transgenes each containing a recognition site for the I-SceI endonuclease, and a tetracycline-inducible I-SceI endonuclease transgene. If interchromosomal HR can be utilized for DSB repair in somatic cells, then I-SceI expression and induction of DSBs within the GFP reporters may result in a functional GFP+ gene. Strikingly, GFP+ recombinant cells were observed in multiple organs with highest numbers in thymus, kidney, and lung. Additionally, bone marrow cultures demonstrated interchromosomal HR within multiple hematopoietic subpopulations including multi-lineage colony forming unit-granulocyte-erythrocyte-monocyte-megakaryocte (CFU-GEMM) colonies. This is a direct demonstration that somatic cells in vivo search genome-wide for homologous sequences suitable for DSB repair, and this type of repair can occur within early developmental populations capable of multi-lineage differentiation.
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PMID:Double-strand break repair by interchromosomal recombination: an in vivo repair mechanism utilized by multiple somatic tissues in mammals. 2434 72