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1. The Master Molecule of Life Dr. Emmanuel Olal MAKENI SCHOOL OF CLINICAL SCIENCES 7/NOV/2017

2. The DNA was discovered in 1953 by James Watson and Francis Crick Throughout the 20th century, many scientists tried to study deoxyribonucleic acid (DNA). In the early 1950s two scientists, Rosalind Franklin and Maurice Wilkins, studied DNA using x-rays . Franklin produced an x-ray photograph that allowed two other researchers, James Watson and Francis Crick to work out the 3D structure of DNA. The structure of DNA was found to be a double helix. The Discovery of the DNA

3. Overview DNA is a long linear polymer that carries information in a form that can be passed from one generation to the next The DNA consist of a large number monomers called nucleotides Each nucleotide is composed of a pentose sugar , a phosphate , and a base (purines and pyrimidines) . Sugars linked by phosphates to form a common backbone The bases vary in sequence along the DNA strand among four kinds (Adenine, Cytosine, Guanine, Thymine) Genetic information is stored in the sequence of bases along a nucleic acid chain

4. Pentose sugar Deoxyribonucleic acid ( DNA) Pentose Sugar is deoxyribose (no OH at 2’ position)

5. Ribonucleic acid ( RNA) Pentose Sugar is Ribose

6. BASES There are two types of bases commonly found in nucleotides: purines and pyrimidines Purines contain two rings and pyrimidines only one ring

7. Nucleotide structure and Nomenclature These are molecules that are assembled to form nucleic acids (DNA and RNA) They consist of three components: a nitrogenous base, a five-carbon sugar (pentose), and a phosphate Five-Carbon Sugars Nucleic acids are classified according to the carbon they contain: if the pentose is ribose, the nucleic acid is RNA; if the pentose is deoxyribose the nucleic acid is DNA 1 2 3 Nucleotide Phosphate Pentose sugar Base

8. Nucleosides and Nucleotides Nucleosides are formed by linking a base to the number 1 carbon of a sugar Carbons of the pentose sugar are labeled with “primes” in nucleotides and nucleosides to differentiate them from the carbons of the purines and pyrimidines

9. Nucleotides Nucleotides are formed when one or more phosphate groups is attached to the 5’ carbon of the nucleoside (nucleoside di- and nucleoside tri-phosphate)

10. Nucleic Acids These are polymers of nucleotides joined by 3’, 5’-phosphodiester bonds; A phosphate group links the 3’ carbon of a sugar to the 5’ carbon of the next sugar in the chain Each strand has a distinct 5’ end and 3’ end thus leading to a polarity The base sequence of a nucleic acid is written by convention in the 5’ 3’ direction

11. DNA structure DNA is a double stranded molecule consists of 2 polynucleotide chains running in opposite directions. Both strands are complementary to each other . The backbone of the molecule is alternating phosphates and deoxyribose sugar The nitrogenous bases are on the inside of the molecules and the 2 chains are joined together by double H-bond between A and T and triple H-bond between C and G. The base pairing is very specific which make the 2 strands complementary to each other. So each strand contain all the required information for synthesis (replication) of a new copy to its complementary.

12. Chargaff’s rule Because of the specific base pairing, the amount of Adenine (A) , equals the amount of Thymine (T) , and the amount of Guanine (G) equals the amount of Cytosine (C) Note, with minor modification (substitution of U for T), these rules also applies to double stranded RNA ( dsRNA ) Using Chargaff’s rule In dsDNA or dsRNA , %A=%T(U ) % G=% C %Purines =% pyrimidines Exercise: A double stranded RNA genome of a virus contain15% uracil, what is the percent of guanine in the genome? Ans-35%

13. The genetic code The bases are arranged in triplets called codons There are 64 codons; 61 code for amino acids, 3 are nonsense codons; they are all written in the 5’ 3 ’ direction A gene is a section of DNA that codes for a particular protein. E ach unique gene has a unique sequence of bases A locus is the location of a gene on a chromosome

14. The Central Dogma The central dogma of molecular biology illustrates the major steps in handling genetic information so that genetic information can be passed along to future generations with integrity.

15. Organization of the DNA Large DNA molecules must be packaged in a manner that enables them to fit inside the cell and still r emain functional Mitochondrial DNA and DNA of most prokaryotes are closed circular structures The molecules may exist as relaxed structures or as supercoiled structures in which the helix is twisted around itself in three-dimensional space Supercoiling results from strain on the molecule caused by under- or over winding the double helix Negatively super coiled DNA: formed if the DNA is wound more loosely than in Watson-Crick DNA; this form is required in biologic reactions Positively supercoiled DNA: formed if the DNA is wound more tightly than in Watson-Crick DNA Topoisomerases: are enzymes that can introduce negative supercoiling in a DNA molecule

16. Nucleosome and Chromatin Nuclear DNA in eukaryotes is found in chromatin associated with histone and nonhistone proteins The basic packaging unit of a chromatin is the nucleosome

17. DNA packaging in Eukaryotic cells