Genetic control of cell function

&PROTEINSYNTHESIS

cell functionof

Nucleic AcidsGenetic Control

Introduction • Cell function is controlled by the DNA

• The DNA determines the kind of proteins that are synthesized in thecell

• These proteins coordinate the process of cell division and they alsodetermine the kinds of metabolic reactions that occur within the cell

• DNA, as well as RNA, is a polymer is made up of monomer units callednucleotides. Many nucleotide join together to form polynucleotidemolecules.

Structure of NUCLEOTIDES• Three major components of nucleotides:

• Pentose sugar: deoxyribose, or ribose sugar• Nitrogenous base: 5 types, divided into two classes, purines and pyrimidines. Purines

are made up of two rings, while pyrimidines have one ring.• Purines: Adenine and Guanine• Pyrimidines: Thymine(only in DNA), Cytosine and Uracil (only in RNA)

• Phosphoric acid

• Nucleotide also serve as part of improtant coenzymes and molecules likeadenosine triphosphate (three phosphate groups), cyclic AMP, coenzyme Aand so on.

• ATP is a phosphorylated nucleotide in that it is made up of Adenine, Ribosesugar, and three phosphate groups.

describe the structure of nucleotides, including the phosphorylated nucleotide ATP (structural formulae are not required)

Adenosine Trisphosphate

describe the structure of nucleotides, including the phosphorylated nucleotide ATP (structural formulae are not required)

Phosphodiesterbonds

• Phosphodiester bonds are strong covalent

bonds that link nucleotides to one another so

as to form polynucleotides

• The 3rd carbon atom of the pentose sugar of

one nucleotide 1 is linked to the phosphate

of another nucleotide 2 by a phosphodiester

bond (this phosphate group is usually

connected to the 5th carbon atom of the

pentose sugar)

Structure of DNA• The DNA is made up of two strands of

polynucleotides joined together by hydrogenbonding between the nitrogenous bases on the twostrands

• The chains are antiparallel to one another, that is,they run in opposite directions

• Each strand forms a right handed helical spiral andthe two chains coil around each other to form adouble helix.

• Each chain has a sugar-phosphate backbone, andthe width between the two backbones is constantand equal to the width of a base pair

describe the structure of RNA and DNA and explain the importance of base pairing and the different hydrogen bonding between bases (include reference to adenine and guanine as purines and to cytosine, thymine and uracil as pyrimidines. Structural formulae for bases are not required but the

recognition that purines have a double ring structure and pyrimidines have a single ring structure should be included

• A base pair is made up of a pyrimidine binding with a purine and thebonds between the bases are specific,• Adenine binds with Thymine, with two hydrogen bonds

• Guanine binds with Cytosine, with three hydrogen bonds

• The two polynucleotide strands are described as complementarybecause this base pairing rule allows the sequence in one chain todetermine the sequence in the other chain.

describe the structure of RNA and DNA and explain the importance of base pairing and the different hydrogen bonding between bases (include reference to adenine and guanine as purines and to cytosine, thymine and uracil as pyrimidines. Structural formulae for bases are not required but the recognition that purines have a double ring structure and pyrimidines have a single ring structure should be included

Purines have two ringsPyrimidnes have one ring

Structure of RNA• RNA is usually a single stranded polynucleotide chain

and there are three types;• Messenger RNA (mRNA)

• Transfer RNA (tRNA)

• Ribosomal RNA(rRNA)

• tRNA and rRNA usuaally assume a more complexstructure while mRNA remains single stranded

describe the structure of RNA and DNA and explain the importance of base pairing and the different hydrogen bonding between bases (include reference to adenine and guanine as purines and to cytosine, thymine and uracil as pyrimidines. Structural formulae for bases are not required but the

recognition that purines have a double ring structure and pyrimidines have a single ring structure should be included

DNA Replication• DNA replication occurs during the S phase of the cell

cycle and it begins at the origins of replication of theDNA

• Each strand of a DNA molecule is used as a templateto make a new strand.

• Step 1: unwinding of the double helix; this is done by the enzyme helicase

• Step 2: single-strand binding proteins attach to theseparated DNA strands and keeps them separatedand untwisted.

describe the semi-conservative replication of DNA during interphase

• Step 2: DNA polymerase binds to exposed strands (thetemplate) and moves/reads in the 3’ 5’ direction and as itmoves, synthesizes a new DNA strand (this synthesis occurs inantiparallel direction, i.e. 3’ 5’).

• Free nucleotides approach the exposed strands and bind withcomplimentary nucleotides following the base pairing rule. TheDNA polymerase forms a strong phosphodiester bond betweenadjacent nucleotides and continues to create a new DNAstrand.

• Thus, DNA polymerase adds new nucleotides to the 3’ end of the growing strand

• Other enzymes involved in the process are: primase,

DNA ligase, topoisomerase

Gene • A gene is a sequence of nucleotides that forms part of a DNA molecule

• It can also be defined as a piece of DNA which codes for a polypeptide

• Genes determine the structural, physiological and biochemical characteristics of an organism

Mutation • A mutation is a change in the sequence

that may result in an altered polypeptide;

state that a polypeptide is coded for by a gene and that a gene is a sequence of nucleotides that forms part of a DNA moleculestate that a gene mutation is a change in the sequence of nucleotides that may result in an altered polypeptide

Mutation • A mutation is a change in the sequence that may result in an

altered polypeptide;

Hemoglobin

• Hb is made up of 4 polypeptide chains: 2 alpha chains(141amino acids long), and 2 beta chains (146 amino acids long)

• A mutation on the gene that codes for the B-chain is thecause of sickle cell anaemia. The fault occurs on the xixthamino acid. In a normal individual, the amino acid is glutamicacid, but in a sickle cell patient, it is replaced by valine.

• Glutamic acid carries a negative charge and it is polarwhereas, valine is non-polar and hydrophobic. This makes theabnormal Hb less soluble when it is deoxygenated.

• When HbS loses its oxygen, it crystallizes into rigid rod-likefibres and this changes the shape of the red blood cells.

• The heterozygous condition is known as sickle cell trait.

describe the way in which the nucleotide sequence codes for the amino acid sequence in a polypeptide with reference to the nucleotide sequence for HbA (normal) and HbS (sickle cell) alleles of the gene for the β-globin polypeptide

Protein Synthesis • A 2-stage process:

• stage 1 is called transcription and it involves the conversion of the basesequence of a section of the DNA representing a gene into thecomplementary base sequence of mRNA.

• Stage 2 is called translation, and I is the mechanism by which the sequence ofbases in a mRNA molecule is converted into a sequence of amino acids in apolypeptide chain.

describe how the information in DNA is used during transcription and translation to construct polypeptides, including the role of messenger RNA (mRNA), transfer RNA (tRNA) and the ribosomes

Transcription

• The DNA double helix unwinds and the nitrogenous bases on the strands of the DNA are exposed.

• One of the strands is selected as a TEMPLATE for the formation of a complementary single strand of mRNA

• Free nucleotides from the cytoplasm and nucleus are used to construct the mRNA molecule according to the base pairing rule. This formation of mRNA is catalysed by an enzyme called RNA polymerase.

• After synthesis, mRNA molecules leave the nucleus via the nuclear pores and they carry the genetic code to the ribosomes

• When a sufficient number of mRNA molecules have been formed, from the gene, the RNA polymerase molecule is detached from the DNA and the two strands of the DNA join up again, reforming the double helix.


Translation

• Occurs on ribosomes (or if several ribosomes are attached to form polyribosome)

• Polyribosome allows for the synthesis of several polypeptide at the same time.

• The first 2 mRNA codons enter the ribosome. An aminoacyltRNA molecule havingcomplementary anticodon and carrying the first amino acid of the polypeptide to besynthesised binds with the mRNA codon. The second codon then also attracts anaminoacyl-tRNA molecule showing the complementary anticodon.

• The ribosome holds the mRNA, tRNA and associated enzymes controlling the process inplace until a peptide bond is formed between adjacent amino acid.

• Once the new amino acid has been added to the growing polypeptide chain, theribosome moves one codon along the mRNA. The tRNA previously attached to thepolypeptide chain now leaves the ribosome and passes back to the cytoplasm to bereconverted to a new aminoacyl-tRNA molecule.

• This continues until the stop codon is reached on the mRNA, and at this point, the mRNAis released from the ribosome and the polypeptide is released for further modificationinto secondary, tertiary or quaternary structures.


The Genetic Code• The sequence of amino acids in the primary

structure of a polypeptide is determined by thesequence of nucleotides in the gene that codes forthat polypeptide.

• This nucleotide sequence is read following theprinciples of the genetic code

• The sequence of nucleotide on the DNAdetermines the sequence of amino acids in apolypeptide, and this in turn determines thestructure and function of the protein

• Before a protein is made, an mRNA molecule isfirst synthesised from the DNA. Thecomplementary triplets in the mRNA are referredto as codons.


The Genetic code• Triplet code; this means that three bases is the code for one amino acid;

the position of an amino acid is determined by a sequence of three codes

• Non-overlapping: no base of a given triplet contributes to part of the codeof the adjacent triplet

• Degenerate: one amino acid can be determined two or more triplet codesor codons.

• Punctuated: some codes act as full stops and they determine the end ofthe code message. They do not code for any amino acid, rather they act as‘stop signals’. Some other codons act as ‘start signals’

• Universal: the same triplet codes for the same amino acids in all livingorganisms


Features of the genetic code

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Genetic control of cell function