BBMB 405 1nd Edition Lecture 25 Outline of Last Lecture XIV Chapter 28 DNA Replication Repair and Recombination B DNA replication proceeds by polymerization of deoxyribonucleoside triphosphates along template A DNA unwinding and supercoiling are controlled by topoisomerases B DNA replication is highly coordinated Outline of Current Lecture XIV Chapter 28 DNA Replication Repair and Recombination C DNA replication is highly coordinated D Many types of DNA damage can be repaired Current Lecture XIV Chapter 28 DNA Replication Repair and Recombination C DNA replication is highly coordinated 1 Points of clarification a Topoisomerase I only part of whole DNA is shown breaks phoshpodiester bond of two ajasent base pairs of entire chromosome changes topography not sequence b An example of Topoisomerase II DNA Gyrase adds negative supercoils 2 DNA polymerase holoenzyme why two core subunits For leading and lagging strand everything is done by one complex 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 3 Replication fork more complicated because move in opposite directions 4 Trombone model all components remain attached to each other DNA polymerase III lets go of lagging strand template aftera adding 1000 neuclotides by releasing sliding clamp and a new loop is form then sliding clamp is reintroduced 5 How is replication replicated E coli a Origin of replication oriC locus contains 5 copies of sequence that are preferred binding sites from origin recognition protein DnaA DnaA monomers bind then form a complex that unwinds DNA unwinding element DUE b DUE AT pairs which are easier to unwind c Rate of DNA synthesis is regulated by the frequency of initiation of DNA replication Dependent on nutrients available physiological challenges DnaA inactivation by ATP hydrolysis DNA methylation d Note that the image in our book of DnaA is not accurate and that the current model is depicted in the lecture notes 6 Bacterial Replication cycle begins at oriC and the replications forks elongate until it reaches the replication termination sequences creating two linked loops catenated DNA then topoisomerase IV unlinks the two DNA strands the termination sequence prevents the relication forks from running into each other 7 Eukaryote Replication a More complicated than bacterial because Eukaryotes have more base pairs and more chromosomes b Cyclin dependent kinase control cell cycle progression c Simplified replication initiation Assembly of origin of replication form hexameric structure Licensing factors recruit helicase that exposes single strand of DNA replication protein A Two polymerases needed to copy eukaryotic replicon polymerase epsilon intiator polymerase begins but soon replaced by more processive enzymes this is called polymerase switching Pol DELTA and Pol alpha primase d Replication bubbles form at multiple origins of replication within chromosomes 8 End of chromosomes a Degradation of RNA ends leads to progressively shorter chromosomes b Telomeres repetitive regions at end of linear chromosomes Protects chromosome end from getting degraded fraying and fusion with neighboring chromsomes Telomeres shorten with every round of cell division due to end replication problem or potentially oxidative stress Correlates with Hayflick limit Senescence onset is linked to telomere shortening c Hayflick limit cells can only divide so many times but after stop dividing remain metabolically active guards against cancer d Telomerase specialized reverse transcriptase that carries its own template plays a role in cancer cell biology and cell aging cancer cells have high levels of telomerase D Many types of DNA damage can be repaired 1 DNA damage a Caused by normal metabolic activities or external factors b If left unchecked it can result in senescence apoptosis or unregulated cell division 2 DNA is not static while replication occurs so it needs to be repaired all the time 3 Cancer cell mutation is usually in DNA repair sequence
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