Structure of DNA
DNA (Deoxyribose Nucleic Acid) is the molecule that stores coded information used by cells.
DNA, along with some protein, makes up the linear chromosomes in all cells in eukaryotes.
In prokaryotes DNA molecules are smaller, circular and not associate with proteins.
Structure of DNA:
DNA (polymer) is made of long chains of units called nucleotides. A nucleotides made up of 3 parts.
Deoxyribose, a 5 carbon sugar
A nitrogen containing organic base, either A,T,G,C.
A phosphate group
Structure of DNA
The nitrogenous bases fall into 2 groups, PURINES and PYRIMIDINES.
Purines are LARGER bases than pyrimidines.
Adenine and Guanine = purines
Thymine and Cytosine = pyrimidines
Purines (2 rings) 1 purine pairs with 1 pyrimidine
Pyrimidines (single rings)
Nucleotides are monomers that join to form polynucleotide strands. The chain is held together because the phosphate group of each nucleotide is linked to the sugar of the next by strong covalent bonds (phosphodiester bonds). As the phosphate group and sugar are identical throughout the chain, this is often termed the sugar-phosphate backbone.
Structure of DNA
The only way in which one polynucleotide chain can differ from another is the sequence of the bases in the polynucleotide.
James Watson and Francic Crick worked out the structure of DNA in the early 1950's at Cambridge University. Their discovery was based on previous research from other scientists including:
- Research to show that the structture was in the form of a helix.
- Studies relating to the relative amounts of purine and pyrmidine bases in several organisms.
A + G = 50%
T + C = 50%
DNA consists of two strands of nucleotides, one running the opposite way to the other (anti-parallel), twisting to form a double helix. The bases of each strand are held together by hydrogen bonding.
Phosphate & sugar = strong covalent bonds (phosphodiester bonds)
Bases = weak Hydrogen bonds
Structure of DNA
Pairing of the bases is COMPLEMENTARY BASE PAIRING.
Adenine forms 2 hydrogen bonds with thymine
Cytosine forms 3 hydrogen bonds with Guanine
Structure of DNA is well suited to its function:
- It is a stable molecule as it is a double helix, and there are many hydrogen bonds. It is also strong due to the covalent bonds in the sugar-phosphate backbone.
- Complementary base pairing allows DNA to replicate itself exactly when cells divide. The weak hydrogen bonds allow strands to separate in this process.
- It is compact. DNA molecules are long, so contain large amounts of coded information. However the double helix shape allows DNA to fit inside the nucleus of the cell.
- Coiling gives the compact shape so DNA can fit inside the cell.
- It has a precise genetic code, determined by the sequence of bases, which controls protein synthesis.
- Double helix provides stability and protects the weak hydrogen bonds.
New cells must have the same DNA code as the parent cells or they would not be able to make the same proteins needed by the cell. Before cells divide their DNA is copied. This process is known as DNA replication and the mechanism by which DNA copies itself is called semi-conservative replication.
Semi-conservative replication: 1 original strand & 1 new strand - each acts as a templace for formation of new nucleotide.
The proccess occurs in the following steps:
- An enzyme, DNA helicase is required to unzip/separate the two strands of a DNA helix, by breaking the weak hydrogen bonds between the strands.
- Each exposed strand of DNA can now act as a template for the formation of a new strand.
- DNA nucleotides line up alongside, and attach to, the exposed bases, by complementary base pairing. New hydrogen bonds form between the bases.
- These new nucleotides are joined together by the enzyme DNA polymerase. Covalent bonds are formed between the nucleotides.
Circular DNA = Prokaryotic = No chromosomes. Linear DNA = Eukaryotic = Chromosomes formed
Attaches the DNA molecules and moves up along its length
Joins the nucleotides to form the new chain. Catalyses formation of phosphate and sugar.
Nucleotides bond by Hydrogen bonds
Evidence for semi-conservative replication
Came from experiments carried out by Meselson and Stahl in 1958, using the bacteria E.coli. These have a single circular DNa molecule and when cultures of these cells were grown in a medium containing the heavy isotope (N15) all the DNA became labelled with N15. These cultures were then transferred to a medium containing the normal light isotope of nitrogen (N14) and allowed to grow. After periods of time, samples were taken and the DNA extracted and centrifuged. (Look in pack for more details&diagram)
Evidence for semi-conservative replication
- Gen 0 = DNA all heavy
- Gen 1 = 2 hybrid molecules of DNA
- Gen 2 = 2 hybrid molecules and two all new 'light' DNA (50% hybrid : 50% light)
- Gen 3 = 2 hybrid molecules and six all new 'light' DNA (25% hybrid : 75% light)
i.e. with each successive gen the proportion of hybrid DNA (N15) halves and all the remaining DNa is 'light' (N14)
Summary of semi-conservative replication
- The two stranders of the DNA molecule are separated
- BOTH strands of the DNA molecule act as a template for the formation of a new complementary strand
- Following replication each new DNA molecule consists of one original ('old') strand and one 'new' strand
A DNA molecule has 2 strands
Genes and polypeptides
A gene is a section of DNA that codes for one polypeptide, and polypeptides in turn determine the nature and development of organisms. A gene occupies a fixed position, called a locus, on a particular chromosome.
How does the gene code for that information:
The specific sequence of bases on 1 strand of DNA controls the sequence of amino acids in proteins (i.e. primary structure) that are made by a cell's ribosomes, and therefore the tertiary structure and function of that protein.
So, differences in the base sequence of alleles of a single gene, e.g. due to mutation, may result in non-functional proteins such as non-functional enzymes:
- The different base sequence leads to...
- A different amino acid sequence (primary structure) which leads to...
- Bonds (hydrogen, ionic and disulphide) forming in different places so there is...
- A different tertiary structure in the protein coded for by that gene.
- If the protein is an enzyme, the active site will change shape, the substrate will not fit and so fewer/no enzyme substrate complexes will form.
Genes and polypeptides
An allele is an alternative form of a gene.
DNA sequence => codes for amino acid sequence (primary structure) => amino acids combine to make tertiary structure of protein
The genetic code
DNA carried the genetic code to allow the cell to make proteins. As enzymes are proteins, and enzymes control all the chemical processes going on inside cells, proteins are vital to a cell's functions.
How does the DNA code for proteins?
The only difference between DNA strands is the number and the sequence of bases.
If 3 bases combine to form a code specifying a particular amino acid, 64 different triplet codes could be coded for.
The genetic code
The code in DNA is therefore a triplet code, meaning that three bases code for one amino acid.
1 base = part of 1 triplet code.
The genetic code has 3 important features:
- The code is non-overlaping - 1 base is only part of 1 triplet code
- The code is degenerate: this means that some amino acids are coded for by more than one triplet. This has arisen because there's 64 different triple codes but only 20 amino acids.
- The code is universal. A given triplet specifices the same amino acid in all organisms.
In eukaryotes much of the nuclear DNA does not code for polypeptides. Non-coding DNA includes sections called INTRONS within genes (non coding DNA) and multiple repeat sequences between genes.
When a gene is 'transcribed' the introns are removed, leaving only the sections that code for proteins (exons)
The nucleus of all eukaryotic cells contain a set number of chromosomes, depending on the species. In humans the chromosomes exist as 23 homologous pairs (each pair consists of a maternal and paternal chromosome). The diploid number of chromosomes is the total number of chromosomes in a normal body cell. The diploid number in humans is 46 (23 from sperm, 23 from egg)
Just prior to the start of cell division the DNA in chromosomes replicates all the way along its length and each chromosome becomes two threads called chromatids, held together at their centromeres. However, they are not visible as individual chromosomes at this stage (DNA still uncoiled).
DNA => mRNA => Amino acid sequence
It's important chromosomes replicate exactly to prevent mutations.
As cell division begins, the chromosomes shorten and thicken (condense) because the DNA coils up more tightly. The chromosomes therefore become clearly visible as separate structures and can be counted.
Diagram of duplicated chromosome:
Chromosomes = Long threadlike structures made of DNA and protein (DNA + protein = chromatin). They contain units called genes.
Homologous chromosomes = A pair of chromosomes containing the same gene sequences in the same positions (loci), each derived originally from a different parent's gamete at fertilisation.
Chromatid = One of the two threadlike strands of a chromosome, formed after DNA replication. Each chromatid in a chromosome is an exact replica of the other (sister chromatids)
Eukaryotic = chromosomes wrapped around histone proteins
Prokaryotic = no chromosomes - coiled and supercoiled.
In mitosis, a parent cell divides to produce 2 daughter cells. Each daughter cell contains an exact copy of the DNA of the parent cell; they are genetically identical.
- Mitosis increases the number of cells during growth
- It replaces the tissue during repair
- It allows asexual reproduction which produces offspring which are genetically identical to the parent. This is ideal when organisms are rapidly establishing a population and variation would be a disadvantage.
In all 3 cases the important point of this method of cell division is that it MAINTAINS THE SAME CHROMOSOME NUMBER FROM ONE GENERATION TO THE NEXT.
Bacteria do not divide by mitosis. They reproduce by a process called binary fission - just split into 2.
The only way variation can arise when a cell divides by mitosis is due to a mutation.
Stages of mitosis (nuclear division)
When a eukaryotic cell divides, the genetic material and nucleus divide first (so 2 new nuclei formed), then the cytoplasm divides to form 2 new daughter cells. Mitosis means 'nuclear division'
Priort to mitosis cells are in a phase called INTERPHASE, during which the cell makes prep for division.
Mitosis itself occurs in a series of stages:
By the end of telophase there will be 2 new nuclei. Immediately following mitosis, division of the cytoplasm occurs (CYTOKINESIS). However this process often begins before mitosis has completed (i.e. during telophase)
Spindle fibres are proteins
Cell is actively synthesising proteins
Chromosomes are not visible prior to mitosis
DNA has replicated
Cell synthesising proteins and increases number of organelles and also ATP production (resp. occuring) - other events occuring during interphase
Nuclear membrane breaks down and nucleolous disappears.
The DNA is free in the cytoplasm.
Chromosomes condense and become shorter. The chromosomes become visible.
Centrioles divide and move to the poles of the cell.
Spindle fibres form across the cell.
At end of prophase the nuclear membrane breaks down so chromosome can use all the space in the cell.
Chromosomes condense & shorten. They become visible. DNA coils,coiling & super coil=become visible
Centromeres hold the chromatids together (definition)
Chromosomes move to the equator of the cell.
Chromosomes attach to the spindle at their centromere.
Metaphase = Middle
During metaphase spindle fibres appear (protein fibres)
Chromosomes attach to spindle fibres at their centromeres at the equator of the cell.
Spindle fibres contract.
The centromeres holding a pair of chromatids together divide.
Sister chromatids are pulled apart.
1 sister chromatid from each chromosomes moves to the opposite poles of the cell.
Anaphase = Apart
Nuclear membrane forms around each group of chromosomes - the cell has 2 nuclei briefly. The nucleolous reforms.
The chromosomes unwind and become diffuse (decondense) and are no longer visible.
Division of the cytoplasm begins with pinching along the equator of the cell.
A new cell membrane forms to form 2 separate cells.
In plants cellulose builds up after to form the cell wall. Division of the cytoplasm begins with pinching along the equator of the cell. Chromatids lie at poles of the cell.
A new nuclear membrane forms around each set of daughter chromosomes.
End of telophase is marked by cytokinesis. Now 2 new nuclei are formed.
Division of the cytoplasm usually follows mitosis fairly quickly. Cells without a cell wall just pinch themselves in 2 and a membrane forms in the middle of the cell.
Eventually, the cell membrane from one side of the cell joins that from the opposite side of the cell and the two new daughter cells separate.
Cells with a cell wall cannot pinch themselves in 2. Instead a new cell wall forms in the middle of the cell.
The cell cycle
Mitosis is usually only a short part of the cycle of events a cell passes through. Each phase of the cycle involves specific cell activities.
1. G1: cells prepare for DNA replication
2. S: DNA replication occurs
3. G2: short gap before mitosis
4. M: mitosis
g1,s,g2 = interphase
Following mitosis, the daughter cells that are produced will then enter phase G1 and the cycle continues.
The duration of interphase gives us info about the rate of cell division. Cells with shorter interphase divide more rapidly (e.g. cancer or skin cells)
bar graph to show units of DNA present in one cell of an organism at the end of diff stages of mitosis.
Following mitosis, the cells of multicellular organisms may differentiate. This means they change to become adapted, or specialised, for specific functions. In early embryos the cells are unspecialised, but have the potential to differentiate into any of 200 specialised cell types that make up the human body.
All cells in an organism are derived from mitotic divisions and therefore have the same set of genes, but in some cells different genes are switched on. i.e. selective activation occurs, e.g. in a nerve cell. genes which allow it to differentiate into this type of cell are turned on.
Advantage of cell differentiation: cells can work together in the form of tissues, tissue can work together in the form of organs, and organs can work together in systems.
Tissue: a group of similar cells with a specific function (muscle tissue,xylem tissue)
Organ: a group of tissues with a particular function (heart)
Organ system: a group of inter related organs (digestive system respiratory system)
Cancer and its treatment
Cancer results from mutations in genes that control cell division, causing rapid, uncontrollable growth and division of cells.
This results in the formation of a mass of abnormal cells (called a tumour or neoplasm).
Cancerous tumuour cells do not respond to signals from nerves and hormones as normal healthy cells would and do not undergo programmed cell death (apoptosis).
In lab conditions, tumour cells differ from normal cells in that they:
- have a large nucleus
- fail to respond to growth regulating processes
Example of how cancer may develop
If the DNA of a cell is faulty or damaged, a protein called p53 normally stops the cell cycle, to prevent the faulty cell from dividing and forming faulty daughter cells. Mutation of the gene coding for this protein can therefore cause cancer to develop in the following way:
- the p53 gene codes for production of the p53 protein
- mutation of the p53 gene means no p53 protein is made (or the protein is non-functional)
- the cell with the damaged DNA completes the cell cycle and continues to divide
- uncontrolled cell division produces cancer
Treatment of cancer
Treatment often involves blocking some part of the cell cycle. Drugs used to treat cancer can disrupt the cell cycle by:
- preventing DNA from replicating (e.g. drug Cisplatin)
- preventing spindle formation e.g. drug vinca alkaloids, or disrupt another stage of mitosis (metaphase)
cancer and its treatment
Cancer treatment drugs pose threats for other cells in that they disrupt the cell cycle of other cells and stop them from dividing.
Cancer cells are more prone to damage by cancer drugs than ordinary cells because they have a much faster rate of division compared to ordinary cells, cancer drugs are more effective against rapidly dividing cells.