MicroBio 160 1st Edition Lecture 10 Outline of Last Lecture I Why screen a Early detection b Warning signs II Types of Tests III Imaging Techniques IV PET scans a Risky V False results VI Sensitivity and Specificity VII Ideal screening VIII Is early detection beneficial IX Treatments X Treatment intent Outline of Current Lecture I DNA Replication II What Happens if the Substitution is not Corrected a Complements and Substitutions b Frameshift Mutation III How else Can Mutations Happen a Chemical Mutagens These 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 Radiation IV Mutations and Cancer a Tumor Suppressor Genes b Proto Oncogenes Oncogenes c DNA Repair Genes V Multi hit Theory and Cancer Genes VI 3 primary families Current Lecture Errors 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 c What 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 synthesis The effect varies Silent mutation mutation that doesn t alter protein function o 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 protein o When it gets to the stop codon makes it stop when you translate the message you no longer have a functionally protein When 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 duplex Complements 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 mutation o When the complement is substituted there is a t instead of a c this may or may 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 different Frame shift Mutation Frame refers to the reading frame of the gene An addition or deletion changes the reading frame For example thesunwashotbuttheoldmandidnotgethishat o 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 Thesunwashotbutgtheoldmandidnotgethishat o 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 either How else can mutations happen Mutations result from mutagen exposure Agent that induces change is mutagen Two types chemical and radiation Chemical 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 molecules Radiation 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 into pieces this causes it to not replicate anymore Double strand breaks often produce lethal deletions o 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 destroyed In 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 produced Common 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 Freckles Mutations 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 cancer o 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 Proto 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 division gene Tumor Suppressor Genes Family of normal genes whose loss or inactivation via mutation can lead to cancer DNA Repair Genes 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 with repair Genes alleles come in pairs one allele can make the tumor suppressor functional Can induce apoptosis repair isn t whose DNA repair genes codeif for proteins effectivefunction is to correct errors that are normal not repaired by the proofreading functions of
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