Medical Biology #2 (PDF) - 6.11.2024

HOW CELLS READ THE GENOME : FROM DNA TO PROTEIN Structure and Function of DNA 6.11.2024 2 6.11.2024  Major groove Minor groove What if it were parallel? Nucleotide 6.11.2024 3  Chromosomal DNA and its Packing 6...

HOW CELLS READ THE GENOME : FROM DNA TO PROTEIN Structure and Function of DNA 6.11.2024 2 6.11.2024  Major groove Minor groove What if it were parallel? Nucleotide 6.11.2024 3  Chromosomal DNA and its Packing 6.11.2024 4 6.11.2024 5  Levels of DNA packing Chromatin Nucleosome 6.11.2024 6 6.11.2024 6  Chromatin is highly dynamic in structure Karyotype, 2X= 46 6.11.2024 6.11.2024 7 What we learned so far? DNA is a double helix which is made up of deoxyribose nucleotides –A,T,G,C Nucleotides : Phosphate + 5 C sugar + Nitrogenous base The two helices run antiparallel to each other The phosphate and sugar constitutes the walls of the DNA DNA is not found naked but rather there is an organizational level of packing. Nucleosome = DNA + histone; Nucleosome + nucleosome = chromatin fiber ; condensed chromatin = chromosome. Typical chromosome is made up of a telomere, a centromere and an origin of replication. 6.11.2024 8  DIFFERENCES BETWEEN DNA AND RNA Cells produce several types of RNA: m-RNA, t-RNA and r-RNA  DNA is transcribed by RNA polymerase In bacteria: One type of RNA polymerase In eukaryotes: Three types of RNA polymerase: RNA polymerase I, II and III The transcription cycle of bacterial RNA polymerase (Bacterial)  TRANSCRIPTION ELONGATION IN EUKARYOTES IS TIGHTLY COUPLED TO RNA PROCESSING  RNA SPLICING ALTERNATIVE SPLICING ABNORMAL PROCESSING OF THE PRIMARY RNA TRANSCRIPT  FROM RNA TO PROTEIN Code Codon Anti-codon Original T-RNA Molecules Match Amino Acids to Codons in m-RNA TRANSCRIPTION ELONGATION PRODUCES SUPERHELICAL TENSION IN DNA DNA gyrase (topoisomerase)  Replication and Repair 6.11.2024 20  DNA replication proceeds with high fidelity but there might occur some mutations! Mutations are difficult to investigate since the deleterious ones are eliminated from the population by natural selection! Some mutations may be silent : may not be deleterious or may not affect the function of the protein! Mutation rates may be protein-specific! 6.11.2024 6.11.2024 21  Semi conservative 5’-3’ direction DNA polymerase It requires both a template and a primer 6.11.2024 22  DNA polymerase serves for two purposes! Proofreading Activities Before the nucleotide binds covalently – If it is not the correct nucleotide then it easily detaches from the strand while the enzyme moves along! After the nucleotide covalently attached – exonucleolytic activity! 6.11.2024 23  5’-3’ direction is required both for elongation and exonuclease activity of DNA polymerase 6.11.2024 25 6.11.2024 26  How is stable DNA double helix unwind ? DNA helicase & single strand DNA binding proteins, Topoisomerase 6.11.2024 27  The proteins at a Replication Fork Cooperate to Form a Replication Machine 6.11.2024 28  Differences between prokaryotic and eukaryotic replication fork 6.11.2024 29  But what happens in chromosomes ? In bacteria (single replication fork, In eukaryotes no nucleosomes & end problems) Packing End problem 6.11.2024 30  End-replication problem at telomeres Problem Solution 6.11.2024 31  DNA Repair: Types of modifications Oxidative damage, Hydrolytic attack, Uncontrolled methylation 6.11.2024 32 Thymine Dimer  The deamination of DNA nucleotides 6.11.2024 33 6.11.2024 33  Chemical modifications of nucleotide if left unrepaired leads to mutation 6.11.2024 34  What we learned so far? DNA replication is semi-conservative and proceeds in 5’-3’ direction DNA polymerase serves for two purposes: polymerization and editing of DNA 5’-3’ direction is required for the exonuclease activity of DNA polymerase Leading and lagging strands – why are they called so? DNA helicase-topoisomerase-single strand binding proteins –primase Difference in replication between bacterial and eukaryotic chromosomes Problem with telomere DNA repair – Types of modifications Why does not DNA have uracil? 6.11.2024 35