Where to find me

1. Where to find me

2. Biochemistry part 1

3. Course outline

4. Popular books

5. More popular books

6. Very short introduction

7. Biological background Ecological SPECIES Physiological ORGANISM Biological CELL Chemical MOLECULE Physical ATOM

8. Molecular biology concepts Role of molecules in cells • Perform various chemical reactions necessary for life => diverse 3D structures necessary • Pass on the instructions for making an organism =>simple 1D medium sufficient Types of molecules in cells • Proteins: 3D structures • DNA: 1D medium • RNA: intermediary between DNA and proteins

9. Cells Humans 60 trillion cells 320 cell types

10. Organisms Classified into two types: • Eukaryotes contain a membrane-bound nucleus and organelles (plants, animals, fungi,…) • Prokaryotes lack a true membrane-bound nucleus and organelles (single-celled, includes bacteria) • Not all single celled organisms are prokaryotes!

11. Chromosomes • In eukaryotes, nucleus contains one or several double stranded DNA molecules organized as chromosomes • Humans: • 22 Pairs of autosomes • 1 pair sex chromosomes

12. Chromosomes

13. Central dogma DNA RNA protein transcription translation

14. deoxyribonucleic acid

15. DNA (deoxyribonucleic acid) The sequence of the human genome has 2.91 billion base pairs (bp) and approximately 35,000 genes. (last count 2003)

16. DNA (deoxyribonucleic acid) Watson & Crick (1953): Nature 25: 737-738 Molecular Structure of Nucleic Acids: a structure for deoxyribose nucleic acid. Nobel Prize, 1962.

17. DNA (deoxyribonucleic acid) Nucleotide: • purine or pyrimidine base • deoxyribose sugar • phosphate group Purine bases • A(denine), G(uanine) Pyrimidine bases • C(ytosine), T(hymine)

18. Structure of DNA 5’ C 20 Å 3’ OH Minor Groove 34 Å 5’ 3’ Sugar-Phosphate Backbone Major Groove 5’ 3’ Nitrogenous Base 3’ 0H C 5’ Central Axis

19. Inter-strand hydrogen bonding (+) (-) (-) (+) to Sugar-Phosphate Backbone Adenine Thymine to Sugar-Phosphate Backbone (-) (+) (+) (-) (+) (-) to Sugar-Phosphate Backbone to Sugar-Phosphate Backbone Guanine Cytosine Hydrogen Bond

20. Inter-strand hydrogen bonding Watson-Crick complement

21. Structure and Nomenclature of Nucleotides Nitrogenous Bases

22. Structure of DNA • Nucleic acids are polynucleotides; • Nucleotides are linked by phosphodiester bridges from 3’ to 5’; • Polymers of ribonucleotides are ribonucleic acids, or RNA; • Polymers of deoxyribonucleotides are deoxyribonucleic acids, or DNA;

23. Sugar backbone

24. Structure of DNA T A G C C 3’ P P P OH P P 5’ Shorthand notation of a nucleic acid 5’ 3’

25. Single stranded polynucleotide 5’GTAAAGTCCCGTTAGC 3’

26. Double stranded polynucleotide 5’GTAAAGTCCCGTTAGC 3’ | | | | | | | | | | | | | | | | 3’ CATTTCAGGGCAATCG 5’

27. Structure of DNA • The B-form is the common natural form, prevailing under physiological conditions of low ionic strength and high degree of hydration. • The Z-form (Zigzag chain) is observed in DNA G-C rich local region. • The A-form is sometimes found in some parts of natural DNA in presence of high concentration of cations or at a lower degree of hydration (<65%).

28. Central dogma

29. Central dogma DNA RNA protein transcription translation

30. Replication of DNA

31. Replication of DNA

32. Replication of DNA • During replication, the DNA helix is unraveled and its two strands are separated. An area known as the replication bubble forms and progresses along the molecule in both direction. Then each DNA strand serves as a template for the synthesis of a new complementary strand. • Each daughter DNA molecule is an exact copy of its parent molecule, consisting of one old and one new DNA strand. Thus the replication is semi-conservative

33. Strand hybridisation A B a b 100° C HEAT A B a b COOL A B a b OR A B a b

34. DNA ligation   ’ ’   ’ ’ ’ ’ Ligase joins 5' phosphate to 3' hydroxyl

35. Restriction endonucleases 5’ P - - OH 3’ EcoRI - P 5’ 3’ OH - HindIII AluI HaeIII

36. DNA polymerase

37. ribonucleic acid

38. RNA (ribonucleic acid) • Similar to DNA • Thymine (T) is replaced by uracil (U) • Forms secondary or tertiary structures • RNA can be: • Single stranded • Double stranded • Hybridized with DNA

39. RNA (ribonucleic acid) • Types of RNAs: • Transfer RNA (adaptor molecule) • Messenger RNA (template for protein synthesis) • Ribosomal RNA (protein synthesis) • Small nuclear RNA (splicesomal RNA) • Small nucleolar RNA (ribosomal RNA processing) • Interference RNA (gene silencing) • microRNA (translation regulation) • Virus RNA (code virus genome) • In comparison with DNA structures, much less is known about RNA structures. Most RNA are associated with proteins which facilitate their structural folding.

40. RNA secondary structure

41. mRNA • Messenger RNA • Linear molecule encoding genetic information copied from DNA molecules • Transcription: process in which DNA is copied into an RNA molecule

42. mRNA processing • Eukaryotic genes can be pieced together • Exons: coding regions • Introns: non-coding regions • mRNA processing removes introns, splices exons together • Processed mRNA can be translated into a protein sequence

43. mRNA processing • Parts List: • mRNA is template • tRNA • ribosomes • amino acids • aminoacyl tRNA transferases

44. mRNA processing

45. Transcription Scientists first 3-D pictures of the "heart" of the transcription machine.

46. Ribosomal RNA Secondary Structure Of large ribosomal RNA Tertiary Structure Of large ribosome subunit Ban et al.,Science289 (905-920), 2000

47. Translation

48. Translation

49. tRNA • Transfer RNA • Well-defined three-dimensional structure • Critical for creation of proteins

50. tRNA • Amino acid attached to each tRNA • Determined by 3 base anticodon sequence (complementary to mRNA) • Translation: process in which the nucleotide sequence of the processed mRNA is used in order to join amino acids together into a protein with the help of ribosomes and tRNA