Molecular base of Inheritance DNA Premedical - biology 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 Streptococcus pneumonie – S strain and R strain 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 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) 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 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. [...]... protects from fusions • telomerase special enzyme • reduction of number of telomeres after each replication • abnormal activity of telomerase in tumor cells 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 ATP powers... 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 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... 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) 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 structural genes Organization of chromatin... another cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity 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+ Flavin adenine dinucleotide - FAD... other strand – lagging s is synthetized discontinuously - Series of segments = Okazaki fragments enzyme DNA Ligase joins them Primase RNA primers Helicase Correction of mistakes • One /10 000bp in replication • DNA polymerase • special enzymes • continuous monitoring and repair • nucleotid excision repair Human chromosomes: 22 pairs of autosomes 1 pair of gonosomes (heterochromosomes) • Karyotype: men 46,... interphase Nucleosome: DNA double helix + histone core • Histone core = octameres of two copies of H2A, H2B, H3, H4 • DNA double helix is winded around the core • spacer segment DNA between two nucleosomes is free or associated with H1 histone (appearance of beads on a string) Condensation of chromatin into chromosomes • String of nucleosomes is coiled into solenoid (6 nucleosomes in each turn) • Solenoid... to ribose Hydrolysis - inorganic phosphate leaves ATP became adenosine diphosphate - ADP The reaction is exergonic High-energy phosphate bonds 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 Guanosine-5'-triphosphate (GTP) •... signal transduction in many different organisms 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 Cyclic guanosine monophosphate - cGMP • is derived from guanosine triphosphate (GTP) • a second messenger much like cyclic AMP • activating intracellular... with loops is coiled into spiral structure of chromatides Karyotype of woman 46,XX – G banding Karyotype of man - 46,XY – G bands Chromosome / in metaphase metacentric submetacentric p telomere centromere q acrocentric satellite sat stalk (NOR) chromatids p = short arm q = long arm NOR = nucleolus organizer region (rRNA genes) Telomeres • multiple repetitions of one short nucleotide sequence TTAGGG [human]... 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