An-Najah National University Genetics: Analysis and Principles Robert J. Brooker Lecture 5 The Structure of DNA Dr. Heba Al-Fares

To fulfill its role, the genetic material must meet four criteria. 1.Information: The genetic material must contain the information necessary to construct an entire organism. 2.Transmission: During reproduction, the genetic material must be passed from parents to offspring. 3.Replication: Because the genetic material is passed from parents to offspring, and from mother cell to daughter cells during cell division, it must be copied. 4.Variation: Within any species, a significant amount of phenotypic variability occurs. 2

Structure of DNA The first essentially correct three-dimensional structure of the DNA molecule was proposed In 1953 James Watson and Francis Crick published a model of DNA structure (the double helix structure). –Their work was based on X-ray crystallography data provided by Maurice Wilkins and Rosalind Franklin. Although DNA is the genetic material of all living cells, some viruses use RNA as their genetic material.

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6 Each spiraling strand, comprised of a sugar- phosphate backbone and attached bases, is connected to a complementary strand by non-covalent hydrogen bonding between paired bases. These two strands run in opposite directions to each other and are therefore anti-parallel.anti-parallel The bases are adenine (A), thymine (T), cytosine (C) and guanine (G). A and G are purines while T and C are pyrimidines A and T are connected by two hydrogen bonds. G and C are connected by three hydrogen bonds. In the DNA molecule, the sum of Purines (A and G) is equal to the sum of the Pyrimidines (T and C)

7 From the roughly equal proportions of these components, Levene concluded correctly that DNA and RNA molecules are made of repeating units of the three components. Each unit, consisting of a sugar attached to a phosphate group and a base, is called a nucleotide. The identity of the base distinguishes one nucleotide from another. The carbon atoms are numbered 1′ to 5′, proceeding clockwise from the oxygen atom; the prime symbol (′) indicates that the number refers to a carbon in a sugar rather than a base

The phosphate and hydroxyl can react chemically with each other. The reaction is a dehydration synthesis, eliminating a water molecule and forming a covalent bond that links the two groups The linkage is called a phosphodiester bond because the phosphate group is now linked to the two sugars by means of a pair of ester (P—O—C) bonds. The two-unit polymer resulting from this reaction still has a free 5′ phosphate group at one end and a free 3′ hydroxyl group at the other, so it can link to other nucleotides.

Chargaff’s Analysis: The four nucleotides were not present in equal proportions in DNA molecules after all. A careful study carried out by Erwin Chargaff showed that the nucleotide composition of DNA molecules varied in complex ways, depending on the source of the DNA. This strongly suggested that DNA was not simple repeating polymer and might have the information encoding properties genetic material must have.

Despite DNA’s complexity, however, Chargaff observed an important underlying regularity in double stranded DNA: the amount of adenine present in DNA always equals the amount of thymine, and the amount of guanine always equals the amount of cytosine. These findings are commonly referred to as Chargaff’s rules: 1. The proportion of A always equals that of T, and the proportion of G always equals that of C: A = T, and G = C. 2. It follows that there is always an equal proportion of purines (A and G) and pyrimidines (C and T).

11 The double helix of the DNA is shown along with details of how the bases, sugars and phosphates connect to form the structure of the molecule.structure of the molecule (Pyrimidines ) (Purines)

12 DNA molecule The distance between two base pairs is 3.4 A ° (Angistrom). Each complete turn of the helix is 34 A ° (10 base pairs). In any segment of the molecule, alternating larger (major grooves) and smaller “minor grooves” are apparent along the axis. The double helix measures 20 A ° (2 nm) in diameter.

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Figure 9.16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H NH N N N G NH 2 H P S P S P 5end 3 H NH 2 N N H H H HH O OO O PCH 2 O H H H OH HH O OO O PCH 2 O H H H HH O OO O P 2 O 2 H H H HH O OO O P O T Key Features Two strands of DNA form a right-handed double helix. The bases in opposite strands hydrogen bond according to the AT/GC rule. The 2 strands are antiparallel with regard to their 5′ to 3′ directionality. There are ~10.0 nucleotides in each strand per complete 360° turn of the helix. 2 nm One nucleotide 0.34 nm One complete turn 3.4 nm T A GC TA P P P P P S S S S S S S S S A C G CG CG GC GC G C GC C P P S P P P P P S S S S S P P P P P P P P P P S S S S S S S S S P S S P P P S S S S P 3 5 G S 3 5 S A P P C TA O N N N N A H H NH 2 N O H N CH 3 H T H H H 2 N N N C O 3end 5 H H HH O OO O PCH 2 O H H H H HH O OO O P 2 O H H HH O OO O P 2 O H H HH O OO O P 2 O HO N O H N CH 3 H T O NH N N N G H 2 N H H H N N N N A H H 2 N H

(b) Space-filling model of DNA(a) Ball-and-stick model of DNA Minor groove Major groove Minor groove Major groove © Laguna Design/Photo Researchers Figure

15 Nucleotides are the building blocks of DNA. Each nucleotide consists of 3 components: - Nitrogen base - Pentose sugar - Phosphate group Nucleotides

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17 There are two kinds of nitrogen bases: 1.Purines: double ringed (include Adinine and Guanine) 2.Pyrimidines: single-ringed (include Thymine, Cytosine, and Uracil). Thymine is specific to DNA and Uracil is specific to RNA. Nitrogen bases

18 Pyrimidines Purines

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20 Pentose sugars Found in RNA Found in DNA

21 Polynucleotides Are formed by the joining of mononucleotides. The linkage between two mononucleotides consists of a phosphate group linked to two sugars forming a phosphodiester bond The phosphate groups link the 3’ carbon of one deoxyribose molecule to the 5’ carbon of the next (3’ – 5’ orientation). Joining of two mononucleotides forms a dinucleotide, joining of three nucleotides forms a trinucleotide and so on.

22 Phosphate group forming 3` - 5` phosphodiester bond

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