Nucleic acid chromosome structure

The nucleic acids were recognized as chemical substances more than 70 years before DNA was found to be responsible for the transmission of inherited characteristics. Later it was suspected that DNA might be the genetic material because of its high concentration in chromosomes and in some viruses. The premise was complicated, however, because the concentration of protein in these structures was... 

Nucleic acid structures and sequences primary and secondary structure of DNA fragments, translocation of genes between two chromosomes, detection of nucleic acid hybridization, formation of hairpin structures (see Box 9.4), interaction with drugs, DNA triple helix, DNA-protein interaction, automated DNA sequencing, etc. 

The genetic information of eukaryotic cells is propagated in the form of chromosomal DNA. Besides the nucleic acid component, chromosomes contain architectural proteins as stoichiometric components, which are involved in the protective compaction of the fragile DNA double strands. Together, the DNA and proteins form a nucleoprotein structure called chromatin. The fundamental repeating unit of chromatin is the nucleosome core particle. It consists of about 147 base pairs of DNA wrapped around a histone octamer of a (H3/H4)2 tetramer and two (H2A-H2B) heterodimers. One molecule of the linker histone HI (or H5) binds the linker DNA region between two nucleosome core particles (Bates and Thomas 1981). 

As in the case of protein structure (Chapter 4), it is sometimes useful to describe nucleic acid structure in terms of hierarchical levels of complexity (primary, secondary, tertiary). The primary structure of a nucleic acid is its covalent structure and nucleotide sequence. Any regular, stable structure taken up by some or all of the nucleotides in a nucleic acid can be referred to as secondary structure. All structures considered in the remainder of this chapter fall under the heading of secondary structure. The complex folding of large chromosomes within eukaryotic chromatin and bacterial nucleoids is generally considered tertiary structure this is discussed in Chapter 24. 

All types of nucleic acids interact with proteins. Chromosomal DNA forms stable nonspecific complexes with structural proteins that stabilize their tertiary structure it also forms transient complexes with enzymes and regulatory proteins that modulate DNA and RNA metabolism. The gross tertiary structure of DNA in E. coli and a typical eukaryotic chromosome is described in the next section. 

From the complementary duplex structure of DNA described in chapter 25, it is a short intuitive hop to a model for replication that satisfies the requirement for one round of DNA duplication for every cell division. In chapter 26, DNA Replication, Repair, and Recombination, key experiments demonstrating the semiconservative mode of replication in vivo are presented. This is followed by a detailed examination of the enzymology of replication, first for how it occurs in bacteria and then for how it occurs in animal cells. Also included in this chapter are select aspects of the metabolism of DNA repair and recombination. The novel process of DNA synthesis using RNA-directed DNA polymerases is also considered. First discovered as part of the mechanisms for the replication of nucleic acids in certain RNA viruses, this mode of DNA synthesis is now recognized as occurring in the cell for certain movable genetic segments and as the means whereby the ends of linear chromosomes in eukaryotes are synthesized. 

Most of the reports about interactions of metals with nucleic acids and their metabolism are based on studies with bacteria and animals. Information from higher plants is rather poor. Ernst (1980) cited an increase of the number of structural chromosome aberrations after cadmium treatment of Crepis capillaris seeds. 

The diseases and disorders chosen for discussion and the order of presentation parallel subject matter taught in most first-year medical biochemistry. Chapters in the first part of the book, Nucleic Acids and Protein Structure, illustrate the relationships of protein structure and function with respect to collagen (Osteogenesis Imperfecta) and hemoglobin (Sickle Cell Anemia). The chapters Fragile X Syndrome and Hereditary Spherocytosis discuss key aspects of DNA and protein structure and their respective role in chromosomal and cytoskeletal structure. The chapter cardiac troponin and myocardial infarction provides an up-to-date demonstration of the usefulness of both structural proteins and enzymes as markers of cardiovascular disease, while the chapter cx Anti trypsin Deficiency discusses the important role of endogenous enzyme inhibitors. 

Viruses do not have a cellular structure. They are particles composed of nucleic acid surrounded by protein some possess a lipid envelope and associated glycoproteins, but recognizable chromosomes, cytoplasm and cell membranes are invariably... 

Phospholipids located in a membrane, phospholipids (as second messengers) in the cytosol, sphingomyelin, folded protein structures, reactive sites of enzymes, nucleic acids in the zinc finger of the chromosome. Wliat are tire assumptions and constraints for each of these molecular modeling systems (a) Force field methods, (b) Semi-empirical method, (c) Ab initio method. 

Chapter 17, which focuses on the structure of the nucleic acids, begins with a description of DNA structure and the investigations that led to its discovery. This is followed by a discussion of current knowledge of genome and chromosome structure, as well as the structure and roles of the several forms of RNA. Chapter 17 ends with the description of viruses, macromolecular complexes composed of nucleic acid and proteins that are cellular parasites. In the following chapter (Chapter 18), several aspects of nucleic acid synthesis and function (i.e., DNA replication and transcription) are discussed. Protein synthesis (translation) is described in Chapter 19. 

From the beads-on-a-string linear topology, research moved to the mapping of genes in a chromosome, and later to the discovery that genes were nucleic acids. Their chemical constitution was then determined, first topologically according to the classic structural theory procedures by Todd, and finally in the three-dimensional structural pattern (3D) of the DNA double helix proposed by Watson and Crick in 1953. 

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