MicroBio 160 1st Edition Lecture 10Outline of Last Lecture I. Why screen?a. Early detectionb. Warning signsII. Types of TestsIII. Imaging TechniquesIV. PET scansa. Risky?V. False results VI. Sensitivity and Specificity VII. Ideal screeningVIII. Is early detection beneficial?IX. TreatmentsX. Treatment intent Outline of Current Lecture I. DNA ReplicationII. What Happens if the Substitution is not Corrected?a. Complements and Substitutions b. Frameshift MutationIII. How else Can Mutations Happen?a. Chemical MutagensThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.b. RadiationIV. Mutations and Cancera. Tumor Suppressor Genesb. Proto-Oncogenes/ Oncogenesc. DNA Repair GenesV. Multi-hit Theory and Cancer Genes VI. 3 primary familiesCurrent LectureErrors are rare, but do happen- When it happens, they can result in a substitution - At the complementary base formula, if one strand already has a g base, then the daughter strand should have a cWhat happens if the substitution is not corrected?Protein DNA polymerase is the enzyme that makes the copy of the parent strand that makes the daughter strand- When the wrong base being inserted—it can back up after proofreading and change the base o If it doesn't then you get the substitution (point mutation) - Point mutation: a substitution that happens during DNA synthesisThe effect varies:- Silent mutation: mutation that doesn’t alter protein functiono Protein has gained a mutation but doesn’t affect their protein function but may or may not change the amino acid function- Missense mutation: different amino acid; resulting protein may have partial function- Nonsense mutation: specifies stop codon; truncated, non functional proteino When it gets to the stop codon, makes it stop—when you translate the message you no longer have a functionally proteinWhen the daughter strand has an incorrect base, it is mismatched to a parent strand—this results in a mismatch repair: we have repair mechanisms that can see that we have an incorrect base (point repair)—this repairs the DNA duplexComplements and Substitutions:- There are other mutations that can happen during DNA replication- A base can be added or deleted by mistake—this causes a frame-shift mutationo When the complement is substituted there is a t instead of a, c (this may ormay not have an effect)- Pink C: insertion so all the amino acids are going to be different- It will not be a functional protein anymore because it has completely changed from what it is supposed to be (frame shift mutation)o All amino acids afterwards are differentFrame-shift Mutation: - “Frame” refers to the reading frame of the gene. An addition or deletion changes the reading frame - For example: thesunwashotbuttheoldmandidnotgethishato Reads: The sun was hot but the old man did not get his hat- If a mutation occurs where another letter is added to the sentences, say “g”, then all the letters to the right of the insertion will shift one position to the right- Thesunwashotbutgtheoldmandidnotgethishato Reads: The sun was hot but gtheoldmandidnotgethisha t Doesn’t make any sense—the deletion of a letter would cause a shift to the left and the sentence would not make sense eitherHow else can mutations happen?- Mutations result from mutagen exposure- Agent that induces change is mutagen- Two types: chemical and radiationChemical mutagens: can cause base substitutions or frame-shift mutations - Alkylating agents: act by adding molecular components to DNA bases thus altering the protein product o If the normal base is c, alkylate changes it to look like a g or a o Since the codon changes, changes message which codes for a different protein- Cross linking agents: create covalent bonds with DNA bases (bind bases together)- Polycyclic aromatic hydrocarbons (PAHs): take into our body, they are inert but once they are metabolized by the human body, they change into other potentially mutagenic moleculesRadiation: Ultraviolet irradiation forms thymine dimers- Covalent bonds between adjacent thymines- Cannot fit into double helix; distorts molecule- Replication and transcription stall at distortion - Cell will die if damage no repaired- X-rays: cause single and double strand breaks in DNA (it can cut the DNA intopieces—this causes it to not replicate anymore- Double strand breaks often produce lethal deletionso If both strands break, your cells don't know what is supposed to go together so they get attached to a chromosome then two genes are destroyedIn the first image: Thymine isn’t able to bind - The DNA and RNA polymerase can't read so whatever protein product was supposed to come from that gene can no longer be producedCommon mutations: - Blue or green eyes: blue eyes have a single, common ancestor according to new research o Scientists have tracked down a genetic mutation that leads to blue eyes—the mutation occurred between 6,000 and 10,000 years ago (before then, there were no blue eyes)- Blonde or red hair- FrecklesMutations and Cancer: alterations in genes involved in controlling cell proliferation and survival fall into 3 main categories- Oncogenes: presence contribute to uncontrolled cell proliferation and leading to cancero Arise from normal proto-oncogenes or viral oncogenes- Tumor suppressor genes: absence (inactivation) contribute to uncontrolled cell proliferation and cancer - DNA Repair Genes: mutations in DNA repair genes lead to lack of DNA repair and can progress to cancer depending on the importance of the protein that is coded for by the mutated geneProto-Oncogenes/Oncogenes:Proto-oncogene: the name of a healthy properly functioning gene—it is only called an oncogene when a mutation occurs and the protein product can no longer function properly- Proto-oncogenes code for proteins that help regulate cell growth and differentiation- When a proto-oncogene is mutated into an oncogene, this oncogene will accelerate cell growth and divisionTumor Suppressor Genes: DNA Repair Genes: Multi-hit Theory and Cancer Genes:- First hit: cell proliferates normally but is carrying mutationFamily of normal genes whose loss or inactivation (via mutation) can lead to cancer- Survey the cell’s daily activities, DNA health, and cell division progression (cell cycle)—Can stop cell division when DNA damage is detected- Can recruit DNA repair proteins to the site of damage and help
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