NUCLEIC ACIDS AND NUCLEOTIDES Lelly Yuniarti , S.Si ., M.Kes

1. Nucleic acids NUCLEIC ACIDS AND NUCLEOTIDESLellyYuniarti, S.Si., M.Kes

2. Why Study DNA? • To truly understand genetics, biologists first had to discover the chemical structure of the gene • This would then help them understand how genescontrol the inherited characteristics of living things • Gene expression is what enables cells of the same organism to take on so many different sizes, shapes andfunctions • (even though just about everycell in an individual contains the same DNA)

3. Review • What organelle is known as the control center of the cell? • What structures are found in the nucleus? • What are short segments of chromosomes? • 4. What are genes/chromosomes composed of? • 5. How do genes/chromosomes control the activity of the cell? nucleus chromosomes genes DNA produce proteins thatregulate cell functions and become cell structures

4. Review Review

5. DNA

6. DNA Function • Scientists wondered how DNA worked. • They knew genes do these critical things: • Carry information from one generation to another • Put information to work to determine an organism’s characteristics • Can be easily copied • Store and transmit genetic information needed for all cell functions • In order to do these things it had to be a special molecule!

7. Understanding DNA • Our knowledge of DNA put to use: • Inheritance/ Genetic Counseling • Cell function/protein synthesis • Embryonic development/gene regulation • Evolution/ phylogenetic relationships • Medicine/genetic diseases • Genetic engineering/ recombinant DNA

8. DNA Package • Chromosomes • 1. Are like books full of sentences • 2. DNA strand twists around and around itself

9. DNA Package • Nucleus • 1. Is like a bookcase • 2. Inside the cell, where all the chromosomes are stored

10. DNA Package • So what would a library full of rows and rows of bookcases represent? • many cells together • which is a tissue

11. Nucleic acids

12. DNA Functions 1. Storage of genetic information 2. Self-duplication & inheritance. 3. Expression of the genetic message. DNA’s major function is to code for proteins. Information is encoded in the order of the nitrogenous bases.

13. I. Bacterial Transformation is Mediated by DNA • Experiment by Frederick Griffith – 1928 • Demonstrated first evidence that genes are molecules • Two different strains of Streptococcus pneumoniae • Non-pathogenic = Avirulent = ROUGH cells (R) • Pathogenic = virulent = SMOOTH (S) • Smooth outer covering = capsule • Capsule = slimy, polysaccharide • Encapsulated strains escape phagocytosis

14. Transformation • Uptake of genetic material from an external source resulting in the acquisition of new traits (phenotype is changed) • Griffith’s expriment was the earliest document evidence of transformation

15. THE NUCLEIC ACIDS (DNA and RNA) Nucleic acids Are formed by the polymerization of a large number of nucleotide units.

16. Nucleic acids

17. NUCLEOTIDES Nucleic acids A nucleotide is a compound that containsa nitrogenous heterocyclic base (a purine or a pyrimidine) connected to a phosphorylated pentose sugar units (deoxyribose or ribose)

18. The bases in nucleosides and nucleotides Nucleic acids The principal purine bases found in the body are adenine (A), and guanine (G) Other purine bases include xanthine and hypoxanthine Pyrimidine bases in the body are cytosine (C), uracil(U) and thymine (T)

19. Nucleic acids

20. Nucleoside and nucleotide nomenclature Nucleic acids Both nucleosides and nucleotides are named after the bases from which they are derived. The nucleosides of ribose with adenine, guanine, cytosine, thymine and uracil are called adenosine, guanosine, cytidine, thymidine and uridine

21. O O N H N H 2 2 N N N N N N 9 1 9 1 N N O N O H N N N N 2 H O H O H O H O O O O O O H O H O H O H O H O H O H O H Uridine Cytidine Guanosine Adenosine Nucleic acids

22. Nucleic acids The corresponding nucleotides are called adenylic acid or adenosine monophosphate (AMP), guanilyc acid or guanosine monophosphate (GMP), cytidilic acid (CMP), uridylic acid (UTP) and thymidic acid (TMP) If the oxyribose is present rather than ribose, the prefix deoxy is used, as in deoxyuridine (dU) or deoxyuridylic acid (dUMP)

23. O O N H N H 2 2 C H 3 N N H N H N N N 1 1 N O N N O N N N O O O O O O O O O O O O P P P P O O O O O O O O O H O H O H H O H H O H O H TMP UMP dAMP AMP Note: The monophosphorylated form of adenosine (adenosine-5'-monophosphate) is written as, AMP. The di- and tri-phosphorylated forms are written as, ADP and ATP, respectively. Nucleic acids

24. Linkage of the base and sugar units Nucleic acids In both nucleosides and nucleotides, the purine or pyrimidine base is linked to the pentose sugar by a glycosidic linkage. The C-1 of the pentose (the anomeric carbon of the D-ribose or 2'-deoxy-D-ribose) is linked to the N-1 of the pyrimidine ring or N-9 the purine ring.

25. Nucleic acids The atoms in the sugar unit are numbered with prime to distinguish the from atoms in the bases. It is important to indicate the position at which esterification of the sugar has occurred e.g.: Adenosine 3′-monophosphate or adenosine 5′-monophosphat. Unless otherwise stated, reference to, for example, and adenine nucleotide in the text implies that is a 5′- ester.

39. Bases, nucleosides, and nucleotides N H 2 N N 9 N N X O H N N N H N N 2 X N H 2 N O N Nucleic acids X

40. O H N O N X O H C H 3 N O N d X Nucleic acids

41. N H N H 2 2 N N N N 9 9 N N N N H O H O O O O H O H O H O H anti -Adenosine syn- Adenosine • Nucleosides are found in the cell primarily in their phosphorylated form. These are termed nucleotides. Nucleic acids

42. Nucleic acids The nucleotides found in DNA are unique from those of RNA in that the ribose exists in the 2'-deoxy form and the abbreviations of the nucleotides contain a d designation. The monophosphorylated form of adenosine found in DNA (deoxyadenosine-5'-monophosphate) is written as dAMP.

43. Nucleic acids

44. Nucleic acids

45. Nucleic acids The nucleotide uridine is never found in DNA and thymine is almost exclusively found in DNA. Thymine is found in tRNAs but not rRNAs nor mRNAs. There are several less common bases found in DNA and RNA. The primary modified base in DNA is 5-methylcytosine. A variety of modified bases appear in the tRNAs. Many modified nucleotides are encountered outside of the context of DNA and RNA that serve important biological functions.

46. Polynucleotides Nucleic acids Polynucleotides (e.g. DNA and RNA) are formed by the condensation of more nucleotides. The condensation most commonly occurs between the alcohol of a 5'-phosphate of one nucleotide and the 3'-hydroxyl group of a second (adjacent nucleotide), with the elimination of H2O, forming a phosphodiester bond.

47. Nucleic acids The formation of phosphodiester bonds in DNA and RNA exhibits directionality. The primary structure of DNA and RNA (the linear arrangement of the nucleotides) proceeds in the 5' ----> 3' direction. The common representation of the primary structure of DNA or RNA molecules is to write the nucleotide sequences from left to right synonymous with the 5' -----> 3' direction as shown: 5'- pG pA pT pC - 3'

48. Nucleic acids Structure of DNA Utilizing X-ray diffraction data, obtained from crystals of DNA, James Watson and Francis Crick proposed a model for the structure of DNA. This model (subsequently verified by additional data) predicted that DNA would exist as a helix of two complementary anti parallel strands, wound around each other in a rightward direction and stabilized by H-bonding between bases in adjacent strands.

49. Nucleic acids

50. Nucleic acids In the Watson-Crick model, the bases are in the interior of the helix aligned at a nearly 90 degree angle relative to the axis of the helix. Purine bases form hydrogen bonds with pyrimidines, in the crucial phenomenon of base pairing.