Lect 1 - The DNA damage response in Ph Pharmacology and...

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The DNA damage response in Ph l d T i l Pharmacology and Toxicology written, directed and produced by: written, directed and produced by J. Peter McPherson Assistant Professor Department of Pharmacology Office: MSB 4308 416 416-978-2727 (I deliver) [email protected]
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Course essentials contact info and office hours no textbook t t i l pre-exam tutorials • tests writing assignment • plagiarism plagiarism Suggested reading
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Why do we need this course? Understanding how cells respond to DNA damage is an emerging important field in pharmacology and toxicology It helps us to understand: 1. the mechanism of action for many antineoplastic agents 2. reasons behind the deleterious effects of environmental agents that cause DNA damage.
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The cellular response to DNA damage: damage a complex network of signaling cascades that culminate i i f th d d DNA in repair of the damaged DNA dividing cells may stop the process of cell division in order to facilitate efficient repair or OR the cell may actively kill itself (apoptosis) following DNA damage Changes in the cell’s ability to either repair DNA or its ability to evade steps leading to apoptosis or cell division arrest can lead to genomic instability and lethality or confer a selective growth advantage to cells leading to cancer
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What is the DNA damage response? oxygen radicals endogenous byproducts ultraviolet light ionizing radiation toxic chemicals in environment antineoplastic agents DNA Cell cycle arrest Apoptosis (cell death) DNA repair Acquisition of mutations and/or chromosomal damage Cancer or lethality
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Review of DNA Concepts: ‘G J ‘Gene Jargon’ DNA:deoxyribonucleic acid DNA:d eoxyribon ucleic a cid RNA:r ibon ucleic a cid t t f th l tid d structure of the nucleotide and components chemical bonds overall structural features
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Nucleotides are the building blocks of DNA (dNTPs) Nucleotides = nitrogenous base + sugar + at least one phosphate group base phosphate(s ) sugar nucleotides (nucleoside mono-, di-, and triphosphates)
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