RESUMO
This review describes a novel type of genome instability, expansion of trinucleotide repeats. Originally discovered in 1991 upon cloning the gene responsible for the fragile X syndrome, it appeared to be a general phenomenon responsible for a growing number of human neurological disorders. Besides apparent medical importance, the discovery of trinucleotide repeat expansion unraveled a fundamental problem of human genetics: a non-Mendelian type of inheritance called anticipation. Understanding the mechanisms of repeat expansion and the molecular pathways leading from these expansions to human diseases became a formidable task for modern biology and one of its spectacular achievements. Here we discuss the major breakthroughs in this field made during the last decade with an emphasis on molecular models of repeat expansion.
Assuntos
Expansão das Repetições de Trinucleotídeos , Animais , HumanosRESUMO
Earlier we have cloned cDNA coding for a polypeptide that reacts with monoclonal antibodies specific for some cytoskeleton structures. This gene is homologous to the laminin receptor 67 KD. However, cDNA suffices only for a polypeptide of 32 Da, far smaller than the 67 rDa laminin receptor. We have constructed a vector that produces the fusion protein LBP-TrpE in the bacterial strain CAG-456. Our studies show that hybrid protein LBP-TrpE is able to interact with laminin. This result was confirmed by using following methods: immunoblotting, "ELISA" and affinity chromatography on laminin.
Assuntos
DNA Circular/genética , Escherichia coli/genética , Expressão Gênica , Laminina , Receptores de Antígenos , Receptores de Laminina , Sequência de Aminoácidos , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , Escherichia coli/crescimento & desenvolvimento , Matriz Extracelular , Humanos , Immunoblotting , Laminina/análise , Proteínas de Fusão Oncogênica/genéticaAssuntos
Laminina/metabolismo , Receptores Imunológicos/genética , Sequência de Aminoácidos , Anticorpos Monoclonais , Sequência de Bases , Clonagem Molecular , Biblioteca Gênica , Projeto Genoma Humano , Humanos , Dados de Sequência Molecular , Ligação Proteica , Receptores Imunológicos/química , Receptores de LamininaRESUMO
By in situ hybridization technique, the mdr gene which is amplified during the development of multiple drug resistance was mapped in the 4q15--21 segment of normal Djungarian hamster chromosome 4. As was shown earlier, this chromosomal region is specific for the location of amplified mdr gene copies. These results, as well as some data obtained by other authors, suggest that recombinations of amplified DNAs occur preferentially in or near the sites bearing homologous sequences.
Assuntos
Cromossomos/ultraestrutura , Colchicina/antagonistas & inibidores , Cricetinae/genética , Amplificação de Genes , Genes , Animais , Células Cultivadas , Bandeamento Cromossômico , Mapeamento Cromossômico , Resistência a Medicamentos/genética , Cariotipagem , Metáfase , Hibridização de Ácido Nucleico , PseudogenesRESUMO
The enzyme termed by us as uridilylpolynucleotide-(5'P----O)-tyrosine phosphodiesterase (Y-pUpN PDE) was isolated from mouse ascites Krebs II cells by ion-exchange and affinity chromatography. The enzyme was found to specifically split the natural covalent bond between VPg and EMC or polio viral RNAs. The enzyme is completely inactivated at 55 degrees C and partially by EDTA. The enzyme preparation isolated by the above-mentioned procedure is not homogeneous and contains inhibiting admixture(s). Possible role of the enzyme in living cells is discussed.