Chromosome function

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  • Chromatin is by its very nature a repressive environment which restricts the recruitment of transcription factors and acts as a barrier to polymerases. Therefore the complex process of gene activation must operate at two levels. In the first instance, localized chromatin decondensation and nucleosome displacement is required to make DNA accessible.

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  • Chapter 12 - The Eukaryotic chromosome. This chapter describes the structure of eukaryotic chromosomes and how that structure affects function. The very long, linear DNA molecules are compacted with proteins in the chromosomes to fit into the nucleus. Several structures are essential for duplication, segregation, and stability.

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  • Malate dehydrogenase (MDH) may be important in car-bohydrate and energymetabolism inmalarial parasites. The cDNA corresponding to the MDHgene, identified on chromosome 6 of thePlasmodium falciparumgenome, was amplified by RT-PCR, cloned and overexpressed in Escherichia coli. The recombinant PfMDH was purified to homogeneity and biochemically characterized as an NAD + (H)-specific MDH, which catalysed reversible inter-conversion of malate to oxaloacetate.

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  • The peptides of the neuropeptide Y (NPY) family exert their functions, including regulation of appetite and circadian rhythm, by binding to G-protein coupled receptors. Mammals have five subtypes, named Y1,Y2 , Y4,Y5 and Y6, and recently Y7 has been discovered in fish and amphibi-ans. In chicken we have previously characterized the first four subtypes and here we describe Y6 and Y7.

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  • Idiopathic Parkinson’s disease (PD) is an age-dependent, neurodegenerative disorder and is predominantly sporadic. Only 20–30% of patients have a positive family history for PD with a complex mode of inheritance. In a few extended families, the disease is inherited as an autosomal dominant trait. Linkage to chromosome 4 was reported in a large Italian kindred multiply affected by an early-onset form of PD (1). However, this finding was not replicated in a sample of 94 Caucasian families by Scott et al. (2), or in 13 multigenerational families by Gasser et al. (3)....

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  • Humanb-defensin-2 (HBD-2) is an antimicrobial peptide produced by the epithelial cells that plays an important role in innate and adaptive immu-nity. Here we report that high mobility group protein N2 (HMGN2), a member of the high mobility group superfamily that affects chromatin function, modulates the expression of HBD-2 in A549 cells treated by lipo-polysaccharide.

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  • Because arsenic is the most prevalent environmental toxin, it is imperative that we understand the mechanisms of metalloid detoxification. In prokary-otes, arsenic detoxification is accomplished by chromosomal and plasmid-borne operon-encoded efflux systems.

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  • HMGN1 is a nuclear protein that binds to nucleosomes and alters the accessibility of regulatory factors to their chromatin targets. To elucidate its biological function and identify specific HMGN1 target genes, we gener-ated Hmgn1–⁄– mice. DNA microarray analysis of Hmgn1+⁄+ and Hmgn1–⁄– embryonic fibroblasts identified N-cadherin as a potential HMGN1 gene target.

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  • The ESSS protein is a recently identified subunit of mam-malian mitochondrial complex I. It is a relatively small integral membrane protein (122 amino acids) found in the b-subcomplex. Genomic sequence database searches reveal its localization to theX-chromosome inhumans andmouse. TheESSScDNAfromChinesehamster cellswas clonedand shown to complement one complementation group of our previously described mutants with a proposed X-linkage. Sequence analyses of the ESSS cDNA in these mutants revealed chain termination mutations. ...

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  • Uncovering Recurrent Submicroscopic Rearrangements As a Cause of Disease For five decades since Fred Sanger's (1) seminal discovery that proteins have a specific structure, since Linus Pauling's (2) discovery that hemoglobin from patients with sickle cell anemia is molecularly distinct, and since Watson and Crick's (3) elucidation of the chemical basis of heredity, the molecular basis of disease has been addressed in the context of how mutations affect the structure, function, or regulation of a gene or its protein product.

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  • The function of microRNAs (miRNAs) is translational repression or mRNA cleavage of target genes by binding to 3¢-UTRs of target mRNA. In this study, we investigated the functions and the target genes of micro-RNA124a (miR124a), and imaged the miR124a-mediated repression of chromosome 14 open reading frame24(c14orf24, unknown function) during neurogenesis, using noninvasive luciferase systems.

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  • There are at least two membrane-bound (HynSL and HupSL) and one soluble (HoxEFUYH) [NiFe]hydrogen-ases in Thiocapsa roseopersicinaBBS, a purple sulfur photosynthetic bacterium. Genes coding for accessory pro-teins that participate in the biosynthesis and maturation of hydrogenases seem to be scattered along the chromosome. Transposon-based mutagenesis was used to locate the hydrogenase accessory genes.

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  • BLASTanalysis of the human and mouse genome sequence databases using the sequence of the human CMP-sialic acid:b-galactoside a-2,6-sialyltransferase cDNA (hST6Gal I, EC2.4.99.1) as a probe allowed us to identify a putative sialyltransferase gene on chromosome 2. The sequence of the corresponding cDNA was also found as an expressed sequence tag of human brain.

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  • Mammalian alcohol dehydrogenases (ADH) 3 form a com-plex enzyme system based on amino-acid sequence, func-tional properties, and gene expression pattern. At least four mouseAdhgenes are known to encode di€erent enzyme classes that share less than 60% amino-acid sequence iden-tity. Two ADH-containing and overlapping C57BL/6 bacterial arti®cial chromosome clones, RP23-393J8 and -463H24, were identi®ed in a library screen, physically mapped, and sequenced.

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  • Telomeres, located at the ends of linear chromosomes, are essential for genome stability and integrity. Advances in telomere researches have linked telomere dysfunction with cellular aging and a number of age-related human diseases. Recent studies further expanded our knowledge of telomere functions - telomeres are shown to be important for microbial pathogen virulence and telomere proteins have important non-telomeric cellular functions.

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  • Genetics is the science of genes, heredity, and the variation of organisms.[37][38] Genes encode the information necessary for synthesizing proteins, which in turn play a large role in influencing (though, in many instances, not completely determining) the final phenotype of the organism. In modern research, genetics provides important tools in the investigation of the function of a particular gene, or the analysis of genetic interactions. Within organisms, genetic information generally is carried in chromosomes, where it is represented in the chemical structure of particular DNA molecules....

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  • RNomics is a newly emerging sub-discipline of genomics that categorically studies the structure, function and processes of non-coding ribo nucleic acids in a cell. MicroRNomics is a sub-field of RNomics that describes the biogenesis and mechanisms of tiny RNA regulators, and their involvement in the processes of development, differentiation, cell proliferation, cell death, chromosomal segregation and metabolism. The discovery of microRNAs in species ranging from Caenorhabditis elegans (C.

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  • Some limited understanding of self-renewal exists and, intriguingly, implicates gene products that are associated with the chromatin state, a high-order organization of chromosomal DNA that influences transcription. These include members of the polycomb family, a group of zinc finger–containing transcriptional regulators that interact with the chromatin structure, contributing to the accessibility of groups of genes for transcription.

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  • While most autosomal dominant inherited cancer syndromes are due to mutations in tumor-suppressor genes (Table 79-1), there are a few interesting exceptions. Multiple endocrine neoplasia type II, a dominant disorder characterized by pituitary adenomas, medullary carcinoma of the thyroid, and (in some pedigrees) pheochromocytoma, is due to gain-of-function mutations in the protooncogene RET on chromosome 10. Similarly, gain-of-function mutations in the tyrosine kinase domain of the MET oncogene lead to hereditary papillary renal carcinoma.

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  • Unequal Crossing-Over Normally, DNA recombination in germ cells occurs with remarkable fidelity to maintain the precise junction sites for the exchanged DNA sequences (Fig. 62-3). However, mispairing of homologous sequences leads to unequal crossover, with gene duplication on one of the chromosomes and gene deletion on the other chromosome. A significant fraction of growth hormone (GH) gene deletions, for example, involve unequal crossing-over (Chap. 333).

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