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Module 5.

6 The sequence of bases in DNA determine the structure of proteins including enzymes Know the definition of a gene Be able to interpret data that the sequence of bases in DNA determines the sequence of amino acids in the polypeptide. Understand that a triplet of bases is needed to code (this is the genetic code) for one amino acid. Understand and explain how the genetic code is universal. Non-overlapping and degenerate. Know the structure and function of mRNA and tRNA and be able to compare these with DNA. Be able to explain how transcription is the production of mRNA using DNA as a template. Understand the role of DNA polymerase. Understand how splicing of pre-mRNA, forms mRNA in eukaryotic cells. Understand the process of translation as the production of polypeptides from the sequence of codons carried by mRNA. Know the roles of ribosomes and tRNA in translation Know that gene mutations can arise during DNA replication via deletion and substitution of bases. Know that mutations occur spontaneously but that the rate of mutation is increased by mutagenic agents. Understand that not all mutations result in change to the amino acid sequence of the encoded polypeptide. Understand how the rate of cell division is controlled by proto-oncogenes that stimulate cell division and tumour suppressor genes which slow cell division. Mutations to these genes may result in uncontrolled cell division.

Key words Transcription, translation, pre-translational modification, splicing genetic code, codon, anticodon, degenerate, mutation, mutagenic agents, base substitution, base deletion, tumour suppressor gene, proto-oncogene. Genetic control of protein structure and function (220-234)

Protein synthesis
RNA o o o mRNA o o Pentose sugar ribose A, G, C + U Phosphate group Long strand arranged in a single helix. mRNA leaves the nucleus via pores in nuclear envelop and enters the cytoplasm, where it associates with ribosomes.

tRNA o relatively small molecule o single stranded

o o o

amino acids can easily attach to the tRNA each tRNA can carry a single amino acid. At the opposite end of the tRNA molecule is a sequence of three other organic bases, known as the anti-codon.

DNA Double polynucleotide chain Largest molecule out of the three Double helix Deoxyribose A, C, T, G Found mostly in nucleus Quantity is constant for all cells of a species (except gametes) Chemically very stable

mRNA Single polynucleotide chain Molecule is smaller than DNA but larger than tRNA Single helix Ribose A, C, U, G Manufactured in nucleus but found throughout the cell Quantity varies from cell to cell and with level of metabolic activity Chemically unstable breaks down easily

tRNA Single polynucleotide chain Smallest molecule of the three Clover-shaped molecule Ribose A, C, U, G Manufactured in nucleus but found throughout the cell Quantity varies from cell to cell and with level of metabolic activity Chemically more stable than mRNA but less stable than DNA

Transcription o Making pre-mRNA, using DNA as a template. o DNA helicase breaks down hydrogen bonds within a specific region of the DNA helix to expose nucleotide bases. o RNA polymerase moves along the two DNA strands, known as the template strand, causing the nucleotides on this strand to join with the individual complementary nucleotides from the pool which is present in the nucleus. o As RNA polymerase adds the nucleotides one at a time to build a strand of pre-mRNA, the DNA strands rejoin behind it. As a result, only about 12 base pairs on the DNA are exposed at any one time.

When the RNA polymerase reaches a particular sequence of bases the DNA that it recognises as a stop triplet code, it detaches, and the production of pre-mRNA is then complete.

splicing of mRNA o DNA is made up of sections of exons that code for proteins and sections called introns which do not. These introns interfere with the synthesis of the polypeptide. In the pre-mRNA of eukaryotic cells, these intervening nonfunctional introns are removed and the functional exons are joined together in a process called splicing. o Once introns have been removed, the remaining exon sections can be rejoined in a variety of combinations. This means that a single section of DNA (gene) can code for up to a dozen different proteins, depending on the order in which the exons are recombined. Mutations can affect the splicing of premRNA. Certain disorders such as Alzheimers disease, are the result of splicing failures that lead to non-functional polypeptides being made.

DNA provides the instructions in the form of a long sequence of nucleotides and the bases they possess A complementary section of part of this sequence is made in the form of a molecule called pre-mRNA a process called transcription.

The pre-mRNA is modified to mRNA by removing the base sequences copied from non-functional DNA (introns) a process called splicing The mRNA is used as a template to which complementary tRNA molecules attach and the amino acids they carry are linked to form a polypeptide a process called translation. Translation o DNA triplets that make up a gene determine the codons on mRNA. The codons on mRNA determine the order in which the tRNA molecules line up. They in turn determine the sequence of amino acids in the polypeptide. In this way genes precisely determine which proteins a cell manufactures. As many of these proteins are enzymes, genes effectively control the activities of the cells.

Gene Mutations Substitution of bases Nonsense mutation o Stop codon mutated o Stopped prematurely

Mis-sense mutation o Arises when the base change results in a different amino-acid being coded for o Different polypeptide chain o Non-functioning

A silent mutation o Degenerate code o Codon changes amino acid is still the same

Deletion of bases Nucleotide is lost from the normal DNA sequence Frame shift

Causes of mutations Spontaneously during replication Random Mutagenic agents o High-energy radiation that can disrupt the DNA molecule o Chemicals that alter the DNA structure or interfere with transcription

Genetic control of cell division Proto-oncogenes stimulate cell division Tumour suppressor genes slow cell division

Role of proto-oncogenes Stimulate cell division Growth factors attach to a receptor protein on the cell-surface membrane and, via relay proteins in the cytoplasm, switch on the genes necessary for DNA replication. A gene mutation can cause proto-oncogenes to mutate into oncogenes o The receptor protein on the cell-surface membrane can be permanently activated, so that cell division is switched on even in the absence of growth factors o The oncogene may code for growth factor that is then produced in excessive amounts, again stimulating excessive cell division

Role of tumour suppressor cells Hereditary cancers Inhibit cell division If this mutates nothing to inhibit cell division therefore tumour.

Proto-oncogenes change into oncogene by mutation. Receptor protein mutates releases chemical without growth factor, so becomes an oncogene and produces a tumour If another proto-oncogene mutates it becomes an oncogene but produces far too many growth factors oncogene causes uncontrollable cell division i.e. produce a tumour. If tumour suppressor gene is mutated, it no longer makes a protein to inhibit cell division

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