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CHAPTER 4 - NUCLEIC ACIDS

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CHAPTER 1: LIPIDS
CHAPTER 2: PROTEINS
CHAPTER 3: CARBOHYDRATES
CHAPTER 4 - NUCLEIC ACIDS
CHAPTER 5: BINDING
CHAPTER 6 - TRANSPORT AND KINETICS
CHAPTER 7 - CATALYSIS
CHAPTER 8: OXIDATIVE-PHOSPHORYLATION
CHAPTER 9 - SIGNAL TRANSDUCTION
Chapter 10: METABOLIC PATWAYS
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A:  THE STRUCTURE OF DNA


adenine


thymine


guanine


cytosine

 

 


DNA is the basic hereditary material in all cells and contains all the information necessary to make proteins.

DNA is a linear polymer that is made up of nucleotide units . The nucleotide unit consists of a base, a deoxyribose sugar, and a phosphate. There are four types of bases: adenine (A), thymine (T), guanine (G), and cytosine (C). Each base is connected to a sugar via a glycosyl linkage. The nucleotide units are connected via the O3' and O5' atoms forming phosphodiester linkages.

In normal DNA, the bases form pairs: A to T and G to C. This is called complementarity. A duplex of DNA is formed by two complementary chains that are arranged in an anti-parallel manner.

The results of fiber and single crystal x-ray crystallographic studies have shown that DNA can have several conformations. The most common one is calledB-DNA. B-DNA is a right-handed double helix with a wide and narrow groove. The bases are perpendicular to the helix axis.

DNA can also be found in theA form in which the major groove is very deep and the minor groove is quite shallow.

A very unusual form of DNA is the left-handed Z-DNA. In this DNA, the basic building block consists of two nucleotides, each with different conformations. Z-DNA forms excellent crystals.

Several years ago it was discovered that nucleic acids can form four stranded structures and a few examples of these molecules now exist. Occasionally mutations occur in which a base is changed. Base pairs still form, but they are not in the usual Watson-Crick geometry.


BDL001

 

Structure of a chromosome

Most people have seen pictures of chromosomes viewed through microscopes. Check out this amazing picture of a chromosome taken form Scientific American, September, 1995.

Chromosomes consist of one dsDNA molecule. Each somatic cell of your body has 23 pairs of chromosomes, one member of each pair contributed by your mother and the other by your father. (In germ cells - eggs and sperm - there are 23 individual chromosomes, not chromosome pairs.)  One pair are the sex chromosomes, which can come in two forms, X and Y. A pair of X's gives a female, and an XY results in a male.

The human genome has about 3-4 billion base pairs of DNA. (I am uncertain if that estimate is for all 23 pairs, or since each member of a pairs is almost identical, it is an estimate of the DNA in one member each of the just 23 different pairs of chromosomes. I will assume that it is for one member of each pair.) Therefore, on average, each single chromosome of a pair has about 150 million base pairs, which consists of one molecule of DNA and lots of proteins bound to it. dsDNA is a highly charged molecule, and can be view, to a first approximation, as a long polyelectrolyte with a large negative. charge. This very large molecule must somehow be packed into a small nucleus. These packing problem is solved by coiling DNA and packing it with proteins, which usually have a net positive charge. The chromosomes are usually dispersed within the nucleus and are not visible with an ordinary microscope. When the cell is ready to divide, the DNA in the chromosomes replicates, and the chromosomes condense in a fashion that they are not visible using an ordinary microscope. At this point the chromosomes can be stained with a variety of stains (hence the name chromosomes), some of which bind differentially to different chromosomes. The different chromosomes can hence be distinquished by their size, shape, and dye-binding properties, the later called a spectralkaryotype analysis of chromosomes.

Figure: spectralkaryotype analysis of chromosomes


Figure:  Human Chromosomes

The standard picture of a chromosome with which you are familiar, including the one shown above, is actually one chromosome of a pair that has just replicated!. One of the chromosomes will stay will the mother cell, and the other will go to the daughter cell. These two chromosomes which are aligned and appear joined at their centers are called sister chromatids.  These large DNA/protein complexes must be further packaged in the nucleus, as shown in the "Carl Saganesque"   reducing view of the chromosome, a double stranded DNA molecule winds around a core of proteins.

Figure:  Packaging of DNA in the Nucleus

The core is called a nucleosome, and can be viewed under an electron microscope if the chromosome is disperesed. The nucleosome consists of 8 positively charge proteins called histones. In the core are 2 copies each of His 2A, 2B, 3, and 4. The dsDNA winds around the nucleosome core about 2.5 times. The dsDNA then links around other nucleosome in whch each nucleosome is connected by a small section of interconnecting spacer DNA, to which is bound another histone, H1. Under an electron microscope, the DNA looks like a bead on a string. The beads are nucleosomes, and the string is the dsDNA.

Figure:  Nucelosome

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