Molecular Biology Lv2 Nucleic Acids Lesson 1 PDF

Molecular Biology Lv2 By Prof. Sami Mohamed Badr University in Cairo, School of Biotechnology Lecture #1 NUCLEIC ACIDS, THE GENETIC CODE, AND THE SYNTHESIS OF MACROMOLECULES CENTRAL DOGMA IN MOLECULAR BIOLOGY:...

Molecular Biology Lv2 By Prof. Sami Mohamed Badr University in Cairo, School of Biotechnology Lecture #1 NUCLEIC ACIDS, THE GENETIC CODE, AND THE SYNTHESIS OF MACROMOLECULES CENTRAL DOGMA IN MOLECULAR BIOLOGY: DNA Transcription RNA (mRNA, rRNA, tRNA) Translation PROTEIN NUCLEIC ACIDS, THE GENETIC CODE, AND THE SYNTHESIS OF MACROMOLECULES STRUCTURE OF NUCLEIC ACIDS 1. Polymerization of Nucleotides Forms Nucleic Acids  STRUCTURE OF NUCLEIC ACIDS 1. Polymerization of Nucleotides Forms Nucleic Acids PURINES PYRIMIDINES  STRUCTURE OF NUCLEIC ACIDS 1. Polymerization of Nucleotides Forms Nucleic Acids Nucleosides (Base + Sugar) Nucleotides (Nucleoside + Phosphate group) One, two, or three phosphate groups esterified at the 5’ carbon  STRUCTURE OF NUCLEIC ACIDS 1. Polymerization of Nucleotides Forms Nucleic Acids When nucleotides polymerize to form nucleic acids, the hydroxyl group attached to the 3’ carbon of a sugar of one nucleotide forms an ester bond to the phosphate of another nucleotide, eliminating a molecule of water: The links between the nucleotides are called phosphodiester bonds.  STRUCTURE OF NUCLEIC ACIDS 1. Polymerization of Nucleotides Forms Nucleic Acids The nucleic acid strand has an end-to-end chemical orientation: the 5’ end has a free phosphate group on the 5’ carbon of its terminal sugar; the 3’ end has a free hydroxyl group on the 3’ carbon of its terminal sugar:  STRUCTURE OF NUCLEIC ACIDS 2. Native DNA Is a Double Helix of Complementary Antiparallel Chains The base-pair complementarity is a consequence of the size, shape, and chemical composition of the bases. Complementary base pairs (Watson-Crick base pairs): G C A T  STRUCTURE OF NUCLEIC ACIDS 2. Native DNA Is a Double Helix of Complementary Antiparallel Chains Two polynucleotide strands can, in principle, form either a right-handed or a left-handed helix  STRUCTURE OF NUCLEIC ACIDS 2. Native DNA Is a Double Helix of Complementary Antiparallel Chains Natural DNA: B form of DNA: Right-handed helix The stacked bases are regularly spaced 0.34 nm apart along the helix axis The helix makes a complete turn every 3.4 nm; thus there are about 10 pairs per turn On the outside of B-form DNA, the spaces between the intertwined strands form two helical grooves of different widths described as the major groove and the minor groove Crystallographic (dehydrated) DNA : A form of DNA: ►11 bases per turn ►the stacked bases are tilted Z DNA ►Short DNA molecules composed of alternating purine- pyrimidine nucleotides (especially Gs and Cs) ►Left-handed ►called Z DNA because the bases seem to zigzag when viewed from the side  STRUCTURE OF NUCLEIC ACIDS 3. DNA Can Undergo Reversible Strand Separation denaturation or “melting” and renaturation Factors: high temperature other agents that destabilize hydrogen bonds, such as alkaline solutions and concentrated solutions of formamide or urea  STRUCTURE OF NUCLEIC ACIDS 3. DNA Can Undergo Reversible Strand Separation Single Strands Melting Temp Depending G-C Double Strands Content  STRUCTURE OF NUCLEIC ACIDS 4. Many DNA Molecules Are Circular  STRUCTURE OF NUCLEIC ACIDS 6. RNA Molecules Exhibit Varied Conformations and Functions  SYNTHESIS OF BIOPOLYMERS: RULES OF MACROMOLECULAR CARPENTRY PROTEINS Proteins and nucleic acids are made up of a limited number of different monomeric building blocks: only 20 different amino acids are used in making proteins only 5 nitrogenous bases are used to construct RNA and DNA The monomers are added one at a time. Each polypeptide and polynucleotide chain has a specific starting point, and growth proceeds in one direction to a fixed terminus. Synthesis of chains begins and ends at well-defined “start” and “stop” signals. Monomer addition proceeds from the amino (NH2-) terminus to the carboxyl (COOH-) terminus in proteins Monomer addition proceeds from the 5’ end to the 3’ end in nucleic acids:  SYNTHESIS OF BIOPOLYMERS: RULES OF MACROMOLECULAR CARPENTRY The primary synthetic product is often modified. Proteins: Nucleic acids: Cleavage Ligation Splicing Cross-Linking  NUCLEIC ACID SYNTHESIS Both DNA and RNA Chains Are Produced by Copying of Template DNA Strands Nucleic Acid Strands Grow in the 5’  3’ Direction g b a phosphates 5’ -P- -P- -P- -OH-3’ + P-P~P- -OH Newly synthesised DNA/RNA chain Nucleoside triphosphate 5’ -P- -P- -P- -P- -OH-3’ + P-P pyrophosphate 5’ 3’ Direction of strain growth  NUCLEIC ACID SYNTHESIS RNA Polymerases Can Initiate Strand Growth but DNA Polymerases Cannot Organization of Genes in DNA Differs in Prokaryotes and Eukaryotes Gene: “a unit of DNA that contains the information to specify synthesis of a single polypeptide chain.” Prokaryotes : OPERONS transcription to form new RNA strands trp (Single) Organization of Genes in DNA Differs in Prokaryotes and Eukaryotes Eukaryotes: many trp Operons Organization of Genes in DNA Differs in Prokaryotes and Eukaryotes Eukaryotic Primary RNA Transcripts Are Processed to Form Functional mRNAs The genetic information of protein coding genes is broken up (discontinuous): Exons - coding sequences Introns - non-protein-coding segments RNA processing: 5’ cap 3’ end polyadenylation Splicing  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS Promoter Translation is the whole process by which the base sequence of an mRNA is used to order and to join the amino acids in a protein.  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 1. Messenger RNA Carries Information from DNA in a Three-Letter Genetic Code 4 nucleotides and 20 possible amino acids: 41 = 4; 42 = 16; 43 = 64 Genetic code is a triplet code. Each triplet is called a codon.  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 1. Messenger RNA Carries Information from DNA in a Three-Letter Genetic Code The genetic code is: a triplet code degenerate, which means that it contains redundancies - synonymous codons : the different codons for a given amino acid Universal The sequence of codons that runs from a specific start site to a terminating codon is called a reading frame.  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 2. The Folded Structure of tRNA Promotes Its Decoding Functions Two-dimensional structure - cloverleaf Three-dimensional structure – L form  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 3. Nonstandard Base Pairing Often Occurs between Codons and Anticodons If perfect Watson-Crick base pairing were demanded between codons and anticodons, cells would have to contain exactly 61 different tRNA species, one for each codon that specifies an amino acid. 30 – 40 different tRNAs in bacterial cells; 61 in animal and plant cells 20 amino acids found in proteins and of 61 codons in the genetic code Consequently: many amino acids have more than one tRNA to which they can attach (explaining how there can be more tRNAs than amino acids); many tRNAs can attach to more than one codon (explaining how there can be more codons than tRNAs).  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 3. Nonstandard Base Pairing Often Occurs between Codons and Anticodons Examples: 2 Phe codons Phe codons UUU and UUC (5’  3’): tRNA GAA (5’  3’) as the anticodon 6 Leu codons Leu codons CUA, CUC and CUU (5’  3’): tRNA (3’-GAI-5’) as the anticodon Leu codon UUA and UUG (5’  3’): tRNA (3’-AAU-5’) as the anticodon Leu codon CUG (5’  3’): tRNA (3’-GAC-5’) as the anticodon  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 4. Aminoacyl-tRNA Synthetases Activate Amino Acids by Linking Them to tRNAs Each tRNA molecule is recognized by one and only one of the 20 aminoacyl-tRNA synthetases. Likewise, each of these enzymes links one and only one of the 20 amino acids to a particular tRNA, forming an aminoacyl-tRNA.  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 4. Aminoacyl-tRNA Synthetases Activate Amino Acids by Linking Them to tRNAs THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 5. Ribosomes Are Protein-Synthesizing Machines  THE THREE ROLES OF RNA IN PROTEIN SYNTHESIS 6. Ribosomes Are Protein-Synthesizing Machines The same parts of each type of rRNA theoretically can form base-paired stem-loops, generating a similar threedimensional structure for each rRNA in all organisms. For example, about 45 stem-loops at similar positions in small rRNAs from many different prokaryotes and eukaryotes are located break time