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Lecture

Lecture22-23.pdf

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Department
Biology
Course
BIOL 205
Professor
Ian D Chin- Sang
Semester
Fall

Description
BIOL 205 week 8 lectures 22 and 23 combinedAn OncogeneInduced DNA Damage Model for Cancer DevelopmentThanos D Halazonetis Vassilis G Gorgoulis Jiri BartekOf all types of DNA damage DNA doublestrand breaks DSBs pose the greatest challenge to cells One might have therefore anticipated that a sizable number of DNA DSBs would be incompatible with cell proliferation Yet recent experimental findings suggest that in both precancerous lesions and cancers activated oncogenes induce stalling and collapse of DNA replication forks which in turn leads to formation of DNA DSBs This continuous formation of DNA DSBs may contribute to the genomic instability that characterizes the vast majority of human cancers In addition in precancerous lesions these DNA DSBs activate p53 which by inducing apoptosis or senescence raises a barrier to tumor progression Breach of this barrier by various mechanisms most notably by p53 mutations that impair the DNA damage response pathway allows cancers to develop Thus oncogeneinduced DNA damagemay explain two key features of cancer genomic instability and the high frequency of p53 mutations oncogenes cancer causing genes induce stalling and collapse at replication forks if DNA pol III encounters blockedd topoisomerase it also stalls which could lead to singledouble stranded breaksBroken chromosomes can arise by insertion of a singlestranded DNA nickany agent that blocks Topoisomerase can result in a single stranded nickeg camptothecina cancer chemotherapy drug nicking function still worked but repair function didntthe single stranded nick can then result in a double stranded breakBAD two pieces can go flying apart in the nucleusDoublestranded breakDoublestrand break repair is essential for lifeneighbouring thymines fuseEukaryotes have a highly ordered chromosome structurenew complexities to DNA synthesisHas to be precise coordinated process all chromosomes need to be replicatedPacking density lets a metre of DNA fit in a cell nucleusView along axis along onee turn of solenoids
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