Nucleic Acids & Protein Synthesis PDF

# Nucleic Acids & Protein Synthesis ## 1. Structure of nucleic acid and replication of DNA ### 1.1 Nucleotides * Nucleic acids such as DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are known as polynucleotides. * Their monomers are known as nucleotides. * Nucleotides are made up of three...

# Nucleic Acids & Protein Synthesis ## 1. Structure of nucleic acid and replication of DNA ### 1.1 Nucleotides * Nucleic acids such as DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are known as polynucleotides. * Their monomers are known as nucleotides. * Nucleotides are made up of three components: * A nitrogen-containing base (also known as a nitrogenous base) * A pentose sugar (containing 5 carbon atoms) * A phosphate group | Properties | DNA | RNA | |------------------------------------------------------|----------------------|--------------------| | **Pentose sugar** | Deoxyribose | Ribose | | **Bases** | Adenine (A) | Adenine (A) | | | Thymine (T) | Uracil (U) | | | Cytosine (C) | Cytosine (C) | | | Guanine (G) | Guanine (G) | | **Number of strands** | Double-stranded (double helix) | Single-stranded | * The nitrogenous base molecules that are found in the nucleotides of DNA (A, T, C, G) and RNA (A, U, C, G) occur in two structural forms: purines and pyrimidines. * The bases adenine and guanine are purines - have a double ring structure. * The bases cytosine, thymine and uracil are pyrimidines - have a single ring structure. * AT has 2 hydrogen bonds. CG has 3 hydrogen bonds. ### ATP * Adenosine triphosphate (ATP) is the energy-carrying molecule that provides the energy to drive many processes inside living cells and is a nucleic acid * It is a phosphorylated nucleotide (involves the addition of a phosphate to an organic compound) and contains pentose sugar and the nitrogenous base adenine. * RNA nucleotide can be combined with one, two or three phosphate groups: * One phosphate group = adenosine monophosphate (AMP) * Two phosphate groups = adenosine diphosphate (ADP) * Three phosphate groups = adenosine triphosphate (ATP) ### 1.2 Structure of DNA * DNA molecules are made up of two polynucleotide strands lying side by side, running in opposite directions - the strands are antiparallel. * Each DNA polynucleotide strand is made up of alternating deoxyribose sugars and phosphate groups bonded together to form the sugar-phosphate backbone. * These bonds are covalent bonds known as phosphodiester bonds. * The phosphodiester bonds link the 5-carbon of one deoxyribose sugar molecule to the phosphate group from the same nucleotide, which is itself linked by another phosphodiester bond to the 3-carbon of the deoxyribose sugar molecule of the next nucleotide in the strand. * As the strands run in opposite directions (they are antiparallel), one is known as the 5' to 3' strand and the other is known as the 3' to 5' strand. * The two antiparallel DNA polynucleotide strands are held together by hydrogen bonds between the nitrogenous bases (DNA base pairs). * These hydrogen bonds always occur between the same pairs of bases: * The purine adenine (A) always pairs with the pyrimidine thymine (T) - two hydrogen bonds are formed between these bases. * The purine guanine (G) always pairs with the pyrimidine cytosine (C) - three hydrogen bonds are formed between these bases. * This is known as complementary base pairing. ### 1.3 Semi-conservative DNA replication * This process occurs before the cell division (mitosis), for the DNA to replicate and provide a copy for the new cell. * This method of replicating DNA is known as semi-conservative replication as in the daughter DNA, one strand is from the parental DNA and one strand is newly synthesised. * **Step 1:** DNA helicase breaks the hydrogen bonds between the complementary base pairs between the two strands within a double helix - causes the parental DNA double helix to unwind. * **Step 2:** Each of the separated parental DNA strands act as a template. Free floating DNA nucleotides within the nucleus are attracted to their complementary base pair on the template strands of the parental DNA. * **Step 3:** DNA polymerase catalyses the bonding of adjacent nucleotides by a condensation reaction between the deoxyribose sugar and phosphate groups of adjacent nucleotides within the new strands (to form phosphodiester bond), creating the sugar-phosphate backbone of the new DNA strands. * DNA polymerase can only build the new strand in one direction (5' to 3' direction). * DNA polymerase moves towards the replication fork in the leading strand away from the replication fork in lagging strand. * Synthesis of leading strand is continuous, but lagging strand is not continuous (synthesise the lagging DNA strand in short segments called Okazaki fragments). * DNA ligase joins these lagging strand segments together to form a continuous complementary DNA strand. * **Step 4:** The two sets of daughter DNA contains one strand of the parental DNA and one newly synthesised strand. ### 1.4 Structure of RNA * RNA (ribonucleic acid) is a polynucleotide - contains the pentose sugar ribose. * It contains the nitrogenous bases - adenine (A), guanine (G), cytosine (C), uracil (U). * Unlike DNA, RNA molecules are only made up of one polynucleotide strand (they are single-stranded). * Each RNA polynucleotide strand is made up of alternating ribose sugars and phosphate groups linked together, with the nitrogenous bases of each nucleotide projecting out sideways from the single-stranded RNA molecule. * The sugar-phosphate bonds (between different nucleotides in the same strand) are covalent bonds known as phosphodiester bonds. * The phosphodiester bonds link the 5-carbon of one ribose sugar molecule to the phosphate group from the same nucleotide, which is itself linked by another phosphodiester bond to the 3-carbon of the ribose sugar molecule of the next nucleotide in the strand. * An example of an RNA molecule is messenger RNA (mRNA), which is the transcript copy of a gene that encodes a specific polypeptide. * Two other examples are transfer RNA (tRNA) and ribosomal RNA (rRNA). ## 2. Protein synthesis ### 2.1 From gene to polypeptide * A gene is a sequence of nucleotides that forms part of a DNA molecule (one DNA molecule contains many genes). * The DNA nucleotide base code found within a gene is a three-letter, or triplet, code - Each triplet codon codes for a specific amino acid- it tells the cell where individual genes start and stop. * There are four bases so there are 64 different triplets possible (4^3), yet there are only 20 amino acids that commonly occur in biological proteins. * This results in multiple codons coding for the same amino acids thus the code is said to be degenerate (this can limit the effect of mutations). * Protein molecules are made up of a series of amino acids bonded together - the shape and behaviour of a protein molecule depends on the exact sequence of these amino acids. ### 2.2 Transcription & Translation * **Transcription** * This stage of protein synthesis occurs in the nucleus of the cell. * Part of a DNA molecule unwinds (the hydrogen bonds between the complementary base pairs break) → exposes the gene to be transcribed. * A complimentary copy of the code from the gene is made by building a single-stranded nucleic acid molecule known as mRNA (messenger RNA). * Free activated RNA nucleotides pair up (via hydrogen bonds) with their complementary bases on one strand (the template strand) of the 'unzipped' DNA molecule (the other strand is called non-template strand). * The sugar-phosphate groups of these RNA nucleotides are then bonded together (phosphodiester bond) by the enzyme RNA polymerase to form the sugar-phosphate backbone of the mRNA molecule. * When the gene has been transcribed (when the mRNA molecule is complete), the hydrogen bonds between the mRNA and DNA strands break and the double-stranded DNA molecule re-forms. * Genes contain exons (code) and introns (don't code). When primary transcript forms it contains both exons and introns, so the introns must be removed. The exons all fuse together to form a continuous RNA molecule (mature mRNA) and the introns are removed. This process is called splicing. * The mRNA molecule then leaves the nucleus via a pore in the nuclear envelope for translation into polypeptide chains. * **Translation** * This stage of protein synthesis occurs in the cytoplasm of the cell. * After leaving the nucleus, the mRNA molecule attaches to a ribosome. * In the cytoplasm, there are free molecules of tRNA (transfer RNA). * tRNA molecules have a triplet anticodon (three unpaired bases) at one end and a region where a specific amino acid can attach at the other (there are 20 different tRNA molecules). * **Translation is the process of making a protein from RNA.** * This process continues until a 'stop' codon on the mRNA molecule is reached - this acts as a signal for translation to stop and at this point the amino acid chain coded for by the mRNA molecule is complete. * This amino acid chain then forms the final polypeptide. ### 2.3 Gene mutation * A gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide (mutations occur continuously). * Causes a change in the structure and function of a polypeptide. * There are different ways that a mutation in the DNA base sequence can occur. * **Insertion of nucleotides** * A mutation that occurs when a nucleotide (with a new base) is randomly inserted into the sequence is known as an insertion mutation. * An insertion of a new triplet codon changes the amino acid that would have been coded for by the original base triplet. * An insertion mutation also has a knock-on effect by changing the triplets (groups of three bases) further on in the DNA sequence - frameshift mutation. * This may dramatically change the amino acid sequence produced from this gene and therefore the ability of the polypeptide to function. * **Deletion of nucleotides** * A mutation that occurs when a nucleotide (and therefore its base) is randomly deleted from the DNA sequence. * A deletion of a triplet codon changes the amino acid that would have been coded for by the original base triplet. * A deletion mutation also has a knock-on effect by changing the groups of three bases further on in the DNA sequence - frameshift mutation. * This may dramatically change the amino acid sequence produced from this gene and therefore the ability of the polypeptide to function. * **Substitution of nucleotides** * A mutation that occurs when a base in the DNA sequence is randomly swapped for a different base. * Unlike an insertion or deletion mutation, a substitution mutation will only change the amino acid for the triplet (a group of three bases) in which the mutation occurs; it will not have a knock-on effect. * Substitution mutations can take three forms: * **Silent mutations** - the mutation does not alter the amino acid sequence of the polypeptide (this is because certain codons may code for the same amino acid as the genetic code is degenerate). * **Missense mutations** - the mutation alters a single amino acid in the polypeptide chain (sickle cell anaemia is an example of a disease caused by a single substitution mutation changing a single amino acid in the sequence). * **Nonsense mutations** - the mutation creates a premature stop codon, causing the polypeptide chain produced to be incomplete and therefore affecting the final protein structure and function (cystic fibrosis is an example of a disease caused by a nonsense mutation, although this is not always the only cause). * **The effect of gene mutations on polypeptides** * Most mutations do not alter the polypeptide or only alter it slightly so that its appearance or function is not changed. * However, a small number of mutations code for a significantly altered polypeptide with a different shape. * This may affect the ability of the protein to perform its function. For example: * If the shape of the active site on an enzyme change, the substrate may no longer be able to bind to the active site. * A structural protein (like collagen) may lose its strength if its shape changes.