topic 8.5

• What is a mutation and what factors increase the rate

  - A change in the DNA base sequence/ often occurs due to errors during DNA replication

  - Mutagenic agents, often external factors such as ionising radiation, chemicals and UV light
• List the types of mutation

  - Translocation = sequence of DNA bases is relocated to another position in the genome e.g. within the same chromosome or to another chromosome

  - Duplication= when one or more bases are repeated/ duplicated

  - Addition= when one or more bases is inserted into the DNA base sequence

  - Deletion= when one or more bases are removed from the DNA base sequence

  - Substitution= when one or more bases is swapped/replaced
• What are frameshift mutations?

  - Mutations that alter the number of DNA bases within the gene

  - Addition, deletion and duplications

  - They can result in the formation of a non-functional protein as they shift the base triplets/codons that follow (change the sequence)
• What are hereditary mutations and what do they often lead to?

  - Genetic disorders

  - Hereditary mutations (passed onto offspring) occur during meiosis and so once the gamete is fertilised the foetus has acquired the mutation which may lead to a disorder
• How do mutagenic agents increase the rate of mutation?

  - Act as base= chemicals known as base analogs may substitute a base/ act as a base resulting in the formation of incorrect DNA

  - Changes the structure of DNA

  - Alter/Delete a base
• What is an acquired mutation?

  - Mutation that occurs in adulthood/ after fertilisation and meiosis
• What is a tumour and what genes control cell division?

  - Tumour = mass of abnormal cells= formed from uncontrollable cell division

  - Proto-oncogenes and Tumour Suppressor genes
• What occurs when there is a mutation in a proto-oncogene/ tumour-suppressor gene and explain their function?

  - A tumour suppressor gene slows cell division= produces a protein which stops cell division or apoptosis (cell destruction) = a mutation results in the gene being inactivated= mRNA is not transcribed, and the protein is not formed= rapid rate of mitosis

  - Proto-oncogene= stimulates cell division = when a mutation occurs = forms oncogene= the gene is overactive and so protein is produced rapidly and so the rate of mitosis is rapid
• What is the difference between benign and malignant tumours?

  - Benign tumour= not cancerous, it does not invade cells and tissues causing damage, it is covered in fibrous tissue which prevents it from invading, however, it can cause blockages and can put pressure on organs

  - Malignant= cancerous= cells can break off and travel through the circulatory system and lymphatic system to invade other cells/causes cell damage
• How do Tumour cells appear differently from normal body cells?

  - Tumour cells have different surface antigens

  - They have a darker nucleus and may have more than one nucleus/ larger nucleus

  - Have an irregular shape

  - Rate of mitosis is greater
• What is methylation?


  - It is the addition of a -CH3- group to a substance

  - It can control whether a gene is transcribed and translated
• How can methylation of proto-oncogene and tumour-suppressor genes form tumours?

  - Proto-oncogene= hypomethylation= gene is overtranscribed

  - Tumour suppressor gene= hypermethylation = gene is not transcribed
• When is a woman exposed to high levels of oestrogen?

  - Near the start of menstruation

  - Starting menopause later than usual

  - Oestrogen-containing drugs
• How can oestrogen cause cancer?

  - Oestrogen can cause breast cells to divide/ stimulate= increased mitosis rate increases the possibility of mutation occurring

  - If a mutation does occur, oestrogen may stimulate its division and so cells with mutation may divide rapidly forming a tumour

  - Oestrogen can also directly introduce mutations to the DNA of breast cells
• What are stem cells?

  - Undifferentiated cells which can form specialised cells in cell differentiation
• where are stem cells they usually found?

  Stem cells are usually found in adult tissue and embryo
• totipotent stem cells


  Stem cells that can differentiate into any type of specialised cells found in organisms of that species.
• pluripotent stem cells


  Stem cells that can become any cell except the cells that make up the placenta
• multipotent stem cells


  stem cells that can become a limited number of types of tissues and cells in the body
• unipotent stem cells


  adult stem cells that give rise to only one specialized cell type
• How do Stem cells differentiate to become specialised?

  - All cells have the same genes/ genetic content, however under different conditions, different genes are expressed, these genes are transcribed into mRNA and then translated into proteins. These proteins modify the cell and determine the cell structure and control cell processes
• What are cardiomyocytes?


  - These are specialised cells found in the muscles of the heart, it was once thought that the heart had no regenerative quality, however the heart tissue had unipotent cells which could be made specialised into these cells/ new cardiomyocytes can be produced.
• Obtaining stem cell methods

  From adult stem cells

  From embryonic stem cells

  iPSC
• promotor region


  Tells enzyme RNA polymerase when to start producing mRNA
• terminator region


  Tells the RNA polymerase to stop adding nucleotides
• What enzyme controls transcription and how is the structure and function of a cell determined?

  - RNA polymerase

  - Different genes are expressed, and so different proteins are produced, modifies the cell, and it determines cell structure and controls cell processes
• What are transcription factors?


  - These are proteins which move from the cytoplasm to the nucleus and binds to promoters/ specific DNA sites on the target gene

  - Transcription factors control the rate of transcription e.g. = ultimately control the expression of a gene

  - Activators= bind to specific DNA sites and help RNA polymerase bind to the start of the target gene = stimulates/ increases rate of transcription

  - Repressors= they stop/ inhibit the rate of transcription= they bind to start of target gene and block RNA polymerase from binding
• What is oestrogen-oestrogen receptor complex?

  - Oestrogen (steroid hormone) can bind with oestrogen receptor (type of transcription factor) to form an oestrogen-oestrogen receptor complex which moves out of the cytoplasm into nucleus where it binds to promoters and helps RNA polymerase attach to target gene

  - Can act as both an activator/ repressor
• How can translation be regulated/ what is used?

  - siRNA used to stop translation in prokaryotes

  - miRNA used to stop translation in eukaryotes e.g. animal and plant cells

  - siRNA is a double stranded RNA strand, and is also known as small interfering RNA
• What is RNAi?


  - RNAi = small-double stranded RNA molecules stop mRNA from target genes being translated into proteins.
• How does siRNA work in prokaryotes and miRNA in plants?

  - The transcribed mRNA moves out from the nucleus into the cytoplasm

  - Double-stranded siRNA molecules associate with proteins (enzymes in the cytoplasm) and are separated into single strands

  - One of the strands are selected and the other strand is degraded, the selected strand binds to the target mRNA strand as a result of complementary base pairing

  - E.g. A pairs with U and C pairs with G

  - The base sequence in siRNA molecules are complementary to the base sequence in sections of mRNA molecules

  - The associated proteins cut the mRNA strand into fragments, these fragments move into a processing body where tools are used to degrade them, and translation is stopped, and protein not produced
• How does miRNA work in mammals/ animal cells?

  - The transcribed mRNA moves out from the nucleus into cytoplasm, the initial miRNA molecules consists of a single long and folded strand which is processed into double-strands and then separated by the enzymes in cytoplasm

  - One of the strands are selected and they associate with proteins, the other strand is degraded

  - A miRNA-protein complex physically blocks translation of target mRNA and the target mRNA is either stored in a processing body or degraded

  - If it is stored it is reused later and translated
• Define epigenetics


  - In eukaryotes, epigenetic control can determine whether a gene is expressed or not

  - Epigenetics are heritable changes to gene function which occur without there being changes to the DNA base sequence

  - Usually occurs as a result of changes to an environment

  - Involves epigenetic marks being placed on DNA base sequence or histone proteins and epigenetic modifications decrease the accessibility of the DNA to transcriptional machinery
• Describe how methylation can lead to a change in DNA?

  - Increased methylation= the addition of CH3 groups at Cpg sites (adjacent bases of cytosine and guanine) causes there to be an change in the structure of the DNA and this prevents the transcriptional machinery from accessing the DNA
• How can decreased acetylation affect DNA?

  - Decrease of COCH3 group being added to histone proteins, the chromatin becomes more condensed and this means it is harder for the transcriptional machinery to access the DNA

  - HDAC (histone deacetylase is responsible for removing acetyl groups from the proteins)
• How can epigenetics play a part into treating disease?

  - Epigenetic changes are reversible

  - Drugs can be manufactured to counteract the epigenetic changes that cause these diseases

  - Decreased acetylation of histones can lead to genes being switched off, HDAC inhibitor drugs can be used to treat such diseases

  - These drugs work by inhibiting the activity of the HDAC enzymes and so the genes remain acetylated and the proteins they could for can be transcribed and translated
• What are the problems with developing drugs to counteract epigenetic changes?

  - These changes take place in lots of cells, so it is important to make sure the drugs are as specific as possible
• What are genome projects?


  - Modernisation of technology has made it possible to sequence the genome of a variety of different living organisms
• How are proteomes sequenced from simple organisms?

  - Simple organisms usually contain little to no introns and these are non-coding sections of DNA, which means that it is easier to determine their proteome from the DNA sequence of their genome
• Why are sequencing proteomes of simple organisms important?

  - It is useful in medical research, in order to determine the identity of particular diseases through their protein antigens and so vaccinations can be developed

  - By determining the proteomes of disease-causing bacteria and viruses also allows the pathogens to be monitored during outbreaks of disease which can lead to better management of the spread of infection and can be used to help identify antibiotic resistance factors