DNA in chromosomes

Figure 36-3. Shown is the extent of DNA packaging in metaphase chromosomes (fop) to noted dupiex DNA (bottom). Chromosomai DNA is packaged and organized at severai ieveis as shown (seeTabie 36-2), Each phase of condensation or compaction and organization (bottom to top) decreases overaii DNA accessibiiity to an extent that the DNA sequences in metaphase chromosomes are aimost totaiiy transcriptionaiiy inert, in toto, these five ieveis of DNA compaction resuit in neariy a 10 -foid iinear decrease in end-to-end DNA iength. Compiete condensation and decondensation of the iinear DNA in chromosomes occur in the space of hours during the normai repiicative ceii cycie (see Figure 36-20).

The nucleus stores the cell s genetic information as DNA in chromosomes. It is bounded by a double membrane but pores in this membrane allow molecules to move in and out of the nucleus. The nucleolus within the nucleus is the site of ribosomal ribonucleic acid (rRNA) synthesis. 

Amdt-Jovin, D.J, Robert-Nicoud, M,Baurschmidt,P., and Jovm, T.M. (1985) Immunofluorescence localization of Z-DNA in chromosomes Quantitation by scanning microphotometry and computer-assisted image analysis. /. Cell BtoL 101, 1422-1433... 

Some examples of moderately repetitive sequences are transposable elements including retroviruses, histone genes that are repeated 30-40 times in the human genome, and genes coding for ribosomal RNAs and transfer RNAs. Most of the moderately repetitive genes do not code for proteins but serve other functions in the cell. Histones are involved in condensation of DNA in chromosomes and both ribosomal RNAs and transfer RNA are involved in protein synthesis. 

DNA in mammalian cells is organized in complex structures called chromosomes (prokaryotes do not have a nucleus, do not divide by mitosis, and do not, strictly speaking, have chromosomes). The DNA in the chromosomes of human and other eukaryotic cells is intimately associated with two classes of proteins called histones and nonhistones. Collectively, DNA, histones, and nonhistones constitute chromatin, from which the name chromosome is derived. The DNA in a chromosome is an extremely long, linear molecule that must be condensed and organized to fit into the chromosomes in the nucleus. (The DNA in the 46 human chromosomes would be about 1 m long if fully extended.) Histones are responsible for the structural organization of DNA in chromosomes the nonhistone proteins... 

Since DNA in chromosomes is a linear molecule, problems arise when replication comes to the ends of the DNA. Synthesis of the lagging strand at each end of the DNA requires a primer so that replication can proceed in a 5 to 3 direction. This becomes impossible at the ends of the DNA and 50-100 bp is lost each time a chromosome replicates. Thus, at each mitosis of a somatic cell, the DNA in chromosomes becomes shorter and shorter. Ultimately, after a limited number of divisions, a cell enters a nondividing state, called replicative senescence, which may play an important role in biological aging. 

About 10-30% of offspring will contain foreign DNA in chromosomes of all their tissues and germ line... 

Pure DNA folds randomly in solution depending on its natural stiffness and the tendency of some sequences to produce bends. B-DNA is quite flexible and a sequence of 200 bp can readily flex through 90°. Stable DNA bends are a common feature of DNA bound to proteins and, in general, when complexed with proteins, DNA takes up specific folded structures which are essential to its function. Examples include the folding of DNA in the nucleosome (Chapter 5) and its interaction with recombination enzymes (Chapter 23). Also, DNA tertiary structure may be important in the control of transcription (Chapter 29). The folding of DNA in chromosomes is a remarkable feat and is discussed further in Chapter 5. 

Chromosomes are made of chromatin which consists mainly of DNA and proteins. RNA is associated with chromatin that is involved in transcription. As mentioned in Chapter 2, the DNA in chromosomes is primarily in a right-handed double helical structure (B-DNA). Chromosomal RNA is mostly the product of ongoing transcription. Chromatin is a complex, dynamic structure determined mainly by protein binding. Many DNA-binding proteins bind independently of the DNA sequence, to a first approximation others have strong preferences for particular sequences. 

While many experiments were suggesting that DNA in chromosomes is very long and continuous, it was established that DNA polymerase adds deoxyribonucleotides to the 3 -hydroxyl terminus of a primer chain and that a DNA template is essential. Why did those investigators interested in DNA replication focus a great deal of attention on determining whether chromosomal DNA contained breaks in the sugar-phosphate backbone ... 

Eukaryotic chromosomes are formed from linear DNA. The DNA is wrapped around specialized proteins known as histone scaffolds then it is folded into loops and is wrapped into minibands, and finally it is stacked as chromosomes. DNA in chromosomes is usually maintained in a slightly negative supercoil (Chap. 8). 

The left-handedness of the mutual twist of DNA in chromosomes has been demonstrated by stereo electron microscopy of dinoflagellate chromosomes (9). 

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