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

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The DNA damage response in Pharmacology and Toxicology ritten, directed and produced by: written, directed and produced by J. Peter McPherson ssistant Professor Assistant Professor Department of Pharmacology Office: MSB 4308 416-978-2727 (I deliver) peter.mcpherson@utoronto.ca
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ourse essentials Course essentials ontact info and office hours contact info and office hours • no textbook • pre-exam tutorials •tests • writing assignment lagiarism plagiarism Suggested reading
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hy do we need this course? Why do we need this course? nderstanding how cells respond to DNA 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 amage: damage a complex network of signaling cascades that culminate 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: ‘Gene Jargon’ NA: oxyribo cleic id DNA:d eoxyribon ucleic a cid RNA:r ibon ucleic a cid structure of the nucleotide and components chemical bonds overall structural features
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Nucleotides are the building blocks f DNA (dNTPs) 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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ucleosides Nucleosides nucleoside = nitrogenous base + sugar base Base Nucleoside (RNA) Deoxynucleoside (DNA) Adenine Adenosine Deoxyadenosine sugar y Guanine Guanosine Deoxyguanosine Cytosine Cytidine Deoxycytidine nucleoside Uracil Uridine (not usually found) Thymine (not usually found) (Deoxy)thymidine
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ases Bases
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ugar Sugar in DNA, the pentose sugar is a 2’-deoxyribose whereas in RNA, the sugar is a ribose in DNA, the primed numbers (e.g. 2’) refer to carbon positions on the sugar, whereas non-primed numbers refer to carbon positions n the base on the base note that the 1’ carbon bonds with the base through an N-glycosidic bond note that the 5’ carbon bonds with the phosphate note that the 3’ carbon also bonds with phosphate except at the “3’ end”
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This note was uploaded on 12/03/2010 for the course PHAMACOLOG pcl470 taught by Professor Arnot during the Fall '10 term at University of Toronto- Toronto.

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

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