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Lecture 08 Replication and Viruses

Lecture 08 Replication and Viruses - Explain the importance...

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Explain the importance of precise DNA replication in preventing the introduction of potentially deleterious changes in the genome Recognize that DNA replication is initiated at replication origins that are activated at different times during the S phase Describe the mechanisms by which normal eukaryotic cells precisely control the initiation of DNA replication at each replication origin Outline: General principles of DNA replication The replication fork Introduction of eukaryotic DNA replication Initiation: Formation of the pre-replication complex in G1 phase of the cell cycle – licensing steps SV40 – a model for eukaryotic replication Telomeres – solving the “end problem” Diseases caused by defects in DNA replication Viral DNA replication strategies o Preparing the host cell o Adenovirus and herpesviruses Therapeutics – inhibitors of DNA replication The Central Dogma o Replication DNA is duplicated from a DNA template Major enzyme: DNA polymerase o Transcription DNA is converted to its mRNA intermediate Major enzyme: RNA Polymerase o Translation mRNA is converted to protein catalysis via: cellular ribosomes and tRNA introduction to DNA replication o cells divide through the coupled processes of mitosis + cytokinesis o cell division requires duplication of the genetic material so both daughter cells receive an identical copy of the individual’s genome o replication is highly regulated process that utilizes many proteins o regulation critical: normal development cancer viral disease DNA synthesis overview o Nucleic acids can only be synthesized 5’-3’ o Nucleotides must be added to a free 3’-OH o NTP is added to the growing chain – it covalently attaches to the 3’ OH and PPi is released in the process o Di-deoxyNTPs will stop the process Bases of many anti-viral drug Adding nucleotide may affect human enzymes also target specific viral enzymes
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o Explain the importance of precise DNA replication in preventing the introduction of potentially deleterious changes in the genome Recognize that DNA replication is initiated at replication origins that are activated at different times during the S phase Describe the mechanisms by which normal eukaryotic cells precisely control the initiation of DNA replication at each replication origin Vocab: di-deoxy NTPs; AZT; Acyclovir (valcyclovir and famciclovir) acridine dyes, okazaki fragments lagging and leading strands, topoisomerase licensing and pre-replication complex primase, clamp and clamp loader, telomerase Werner syndrome, blooms syndrome Outline: General principles of DNA replication The replication fork Introduction of eukaryotic DNA replication Initiation: Formation of the pre-replication complex in G1 phase of the cell cycle – licensing steps SV40 – a model for eukaryotic replication Telomeres – solving the “end problem”
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