Current LectureMCB 250 1st Edition Lecture 19Outline of Current Lecture 1. Spontaneous Mutation2. Tautomerism3. Misalignment4. Cytosine5. Purine6. Oxidative DNA Damage7. UV light8. Chemical ModificationCurrent Lecture1. Spontaneous Mutation- Due to the result of tautomerization and misalignment- Chemical instability of DNAo Deamination of Co Bases can fall off spontaneously- Oxidative DNA damageo Modified baseso Single and double stranded breaks2. Tautomerism- Aromatic rings with certain electron structure associated with them. They can move around and at some frequency can alter electron structure. The double bond can changeand causes one proton to leave and another proton can come in. The difference is the arrangement of the electrons in the double bond- The shifts of electrons change the base pair properties of the base. The stable structure if you take a snapshot of all adenines, some fractions will be in the other state.- C in the imino form can base pair with A. Due to the inherent chemistry of the bases, thepolymerase will, at some frequency, incorporate the wrong base. It thinks it’s a good bp.- Doesn’t mean the mutation is fixed in the genome. 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.- Not until it is replicated again that one strand can be wild type, but new strand is mutant. - The base pair will actually stabilize the form of the C. - Tautomeres exist and changes the base pairing properties- Until there is a second round of replication, the mutation is not fixed and can be fixed.3. Misalignment- Occurs when there are repeating sequences of nucleotides4. Cytosine- Spontaneously deaminates and gives uracil- Inherint chemical unstability in the DNA: nothing you can do about it. It happens. C-> U- There should not be Uracil in the DNA. 5. Purines- Will spontaneously hydrolyze- N-glycosidic bond is unstable, and the base will simply fall off- Abasic (without a base) or apurinic site. Inherent chemical instability of DNA, can’t do anything about it. - In any moment in your cell, there is 1000 abasic sites- Polymerase will not know what to do because there are no base pairs to base pair with.6. Oxidative DNA Damage- Oxygen can be mutagen- Oxygen can serve as a terminal electron acceptor in respiration.- Normally add 4 electrons and hydrogen to oxygen to get water- Oxygen can run into molecules in the cell and pick up one electron at a time- Side products of Oxygen can be formed and be very toxico Superoxide, Hydroxyl radical can react with any biological molecule.- OH can create double stranded, single stranded Breaks in the DNA- Open up phosphodiester bond and react with sugar itself and break the sugar. - More dramatic breaks in the DNA/ sugar would cause a replication blockage with polymerase. When it gets there, the polymerase wouldn’t know how to deal with the structure7. UV Light- Causes thymine dimers- The bases absorb energy and their electrons are kicked up into another state. If there are two thymines next to each other, they can interact with one another and form a cyclobutane ring from the double bonds. - This interferes base pair properties and creates a structure for when DNA pol gets there it cannot do anything.- During replication, the one base is in the active site, and the template strand is bent and out of the way so the next base is not in the way. If the bases are crosslinked, it cannot bend anymore, it is a block to replication.- Thymine dimers: products of UV light damage8. Chemical modification- Alkalyating agents: things found in manufacturing products, cigarette smoke, exhaust. - Change base pair properties of the