Molecular base of Inheritance DNA

1. Molecular base of Inheritance DNA Premedical - biology

2. Proof that DNA is carrier of genetic information - 1928 Griffith‘s experiment - Bacterial transformation Recombination of bacterial genetic material by transmission of naked DNA into recipient cells Avery, McLeod, McCarthy (1944) – the same effect with isolated DNA

3. Streptococcus pneumonie – S strain and R strain

4. 1953 - James D. Watson a Francis Crick • used x-ray diffraction data collected by Rosalind Franklin • proposed the double helix as the threedimensional structure of DNA • the main role is the long-term storage of information • ability to manage its own replication • DNA manage the development of biochemical, anatomical and physiological and behavioral traits of all known living organism

5. Monomers - nucleotides: organic molecule called a nitrogenous base, a pentose (five-carbon sugar) and phosphate group Two families of nitrogenous bases: pyrimidines, purines Pyrimidine has a six-membered ring of cabron and nitrogen; Cytosine (C), Thymin (T) and Uracil (U) Purins the six-membered ring fused to a five-membered ring Adenin (A), Guanin (G)

6. Bases - Adenine, guanine and cytosine are found in both types of nucleic acid. Thymine is found only in DNA and uracil only in RNA. Sugars - Ribose in nucleotides of RNA Deoxyribose in DNA Nucleoside - nitrogenous base joined to sugar

7. Nucleotides are bonded by covalent bonds called phosphodiester linkages between phosphate of one and the sugar of the next. Two polynucleotides spiral around imaginary axis to form double helix Two polynucleotides are held by hydrogen bonds between the paired bases and by van der Waals attractions between the stacked bases.

9. DNA molecules - thousands or millions of base pairs Adenine always pairs with thymine, Guanine always pairs with cytosine. Two strands of double helix are complementary and are antiparallel. In preparation for cell division, each strand serves as a template to order nucleotides into a new complementary strand = Semiconservativereplication

10. Cell cycle

11. Replication • Origins of replication • circular bacterial chromosome has a single origin • Replication starts in many places (Eukaryotes) simultaneously and asynchronnous • DNA replication proceeds in both direction • At each end of replication bubble is replication fork • DNA polymerase – addition of nucleotides only to the free 3‘ end, new strand can elongate only in one direction (5´→ 3´)+ and correction of mistakes

12. A new strand in direction 5´→ 3´ leading strand The other strand – lagging s. is synthetized discontinuously - Series of segments = Okazaki fragments enzyme DNA Ligase joinsthem Primase - RNA primers Helicase

13. Correctionof mistakes • One /10000bp in replication • DNA polymerase • special enzymes • continuous monitoring and repair • nucleotid excision repair

14. Human chromosomes: 22 pairs of autosomes 1 pair of gonosomes (heterochromosomes) • Karyotype: men 46, XY, women 46, XX Euchromatin • despiralized in interphase • spiralized in mitosis • contains structural genes

15. Heterochromatin – repetitive sequences Constitutive – centromers of all chromosomes Facultative - structurally euchromatin, but behaves as heterochromatin = one of two X chromosomes in women = genetically inactive = X chromatin (sex chromatin= Barr body)

16. Ultrastructure of chromosomes • DNA • Histones – basic proteins H1,H2A, H2B,H3,H4 • Non-histone proteins The whole length DNA cca 2 m human genome contains cca 30 000 structuralgenes

17. Organization of chromatin in interphase Nucleosome: DNA double helix + histone core • Histone core = octameres of two copies of H2A, H2B, H3, H4 • DNAdouble helixis windedaround the core • spacer segment DNA between two nucleosomes is free or associated with H1 histone (appearance of beads on a string)

20. Condensation of chromatin into chromosomes • String of nucleosomes is coiled into solenoid(6 nucleosomes in each turn) • Solenoid is packed into loops attached to the nonhistone protein scaffold (Laemli loops) • nonhistone protein scaffold with loops is coiled into spiral structure of chromatides

22. Karyotype of woman 46,XX – G banding

23. Karyotype of man - 46,XY – G bands

24. p telomere centromere satellite sat. stalk (NOR) q chromatids Chromosome / in metaphase metacentric submetacentric acrocentric p = short arm q = long arm NOR = nucleolus organizer region (rRNA genes)

25. Telomeres • multiple repetitions of one short nucleotide sequence TTAGGG [human] • telomeric DNA protects genes from being eroded, protects from fusions • telomerase special enzyme • reduction of number of telomeres after each replication • abnormal activity of telomerase in tumor cells

27. Nucleotides • are structural units of RNA and DNA • serve as sources of chemical energy: ATP, GTP • participate in cellular signaling: cAMP, cGMP • are incorporated into important cofactors of enzymatic reactions: CoA, FAD, FMN, and NADP

28. ATP powers cellular work • multifunctional nucleotide used in cells as a coenzyme • "MOLECULAR UNIT OF CURRENCY" of intracellular energy transfer • produced by photophosphorylation and cellular respiration • used in many cellular processes, including biosynthetic reactions, motility, and cell division.

29. ATP - closely related to one type of nucleotide found in nucleic acid [base adenine bonded to ribose] • in RNA one phosphate group is attached to the ribose • chain of three • phosphategroups • attached to ribose

30. Hydrolysis - inorganic phosphate leaves ATP became adenosine diphosphate - ADP The reaction is exergonic High-energy phosphate bonds

31. Cyclic adenosine monophosphate (cAMP) is a second messenger important in many biological processes. cAMP is derived from adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms.

32. Guanosine-5'-triphosphate (GTP) • a substrate for the synthesis of RNA during transcription and a source of energy for protein synthesis • a source of energy or an activator of substrates in metabolic reactions

33. Cyclic guanosine monophosphate - cGMP • is derived from guanosine triphosphate (GTP) • a second messenger much like cyclicAMP • activating intracellular protein kinases

34. Nicotinamide adenine dinucleotide, abbreviated NAD+ • is a coenzyme found in all living cells • NAD+ is involved in redox reactions, carrying electrons from one reaction to another. cofactoris a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity

35. Nicotinamide adenine dinucleotide phosphate (NADP+) • is used in anabolic reactions • NADPH is the reduced form of NADP+ • NADP+ differs from NAD+ by the • presence of an additional • phosphate group on the 2' position • of the ribose ring in NADP+

36. Flavin adenine dinucleotide - FAD • is a redox cofactor involved in several important reactions • in metabolism • FAD can exist in two different redox states. • The molecule consists of • a riboflavin moiety (vitamin B2) • bound to the phosphate group of • an ADP molecule.

37. Flavin mononucleotide (FMN) • is a biomolecule produced from riboflavin (vitamin B2) • acts as prosthetic group of various oxidoreductases including NADH dehydrogenase. tightly-bound cofactors termed prosthetic groups

38. Coenzyme A (CoA, CoASH, or HSCoA) • is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids • the oxidation of pyruvate in the citric acid cycle

39. Alternate DNA structures DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms. only B-DNA and Z-DNA have been directly observed in functional organisms. From left to right, the structures of A, B and Z DNA

40. Campbell, Neil A., Reece, Jane B., Cain Michael L., Jackson, Robert B., Minorsky, Peter V., Biology, Benjamin-Cummings Publishing Company, 1996 –2010.