PCL477H1-Lecture 5a to post - Lecture 5 overview

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Lecture 5 overview concept of DNA double-strand breaks (DSB) strand breaks produced by clastogenic agents strand breaks produced by endogenous processes pathways of double-strand break repair pathways single-strand break repair how can we study strand break repair consequences of defective double-strand break repair
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DNA Strand break concept damage to DNA bases -potential to alter coding  information in the genome - mutagens : agents that result in  DNA base damage damage to the DNA double-helix  backbone -fracture of the sugar-phosphate  backbone      clastogens:  agents that result in  DNA backbone damage
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Double-strand breaks How are they formed? (gimme a break) 1. Naturally occurring DNA transactions Te lo m e re s  – c hro m o s o m e  te rm ina ls   DNA re a rrang e m e nts  in the  im m une  s ys te m   Exc hang e  o f g e ne tic  info rm atio n b e twe e n ho m o lo g o us  c hro m o s o m e s 2. DNA backbone damage by radiation or chemicals alkylatio n o f pho s pha te s o xidative  dam a g e  to  s ug a rs   3. DNA damage that results in compromised or failed replication of DNA or segregation of DNA e .g . S talling  and c o llaps e  o f re plic atio n fo rks  – s ing le - and do uble -s tra nd  bre a ks  induc e d whe n DNA re plic a tio n fo rk e nc o unte rs  a  dam a g e d te m pla te / s ing le -s tra nde d bre a k in the  te m plate e .g . s e g re g atio n o f da ug hte r c hro m o s o m e s  during  a naphas e  m a y re s ult in  DS Bs  due  to  m e c hanic a l s he a ring  o f c ro s s -linke d DNA
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DNA strand breaks caused by antineoplastic drugs and xenobiotics Alkylation of phosphates groups in DNA backbone: -a ny alkyla ting  ag e nt that c a n re a c t with DNA b as e  has  po te ntial fo r c re a ting   a dduc t with pho s phate  g ro up Oxidative damage to DNA sugars: -a bo ut 20%  o f hydro xyl radic als  tha t re a c t with DNA atta c k the  s ug a rs  in the   b ac kb o ne e .g . 1-G y do s e  o f io nizing  ra diatio n c a n re s ult in 600 to  1000 s ing le -s trand b re a ks   a nd 16 to  40 do uble -s trand b re a ks
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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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PCL477H1-Lecture 5a to post - Lecture 5 overview

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