cancer2008-3 - Recombination and Cancer Two forms of...

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Unformatted text preview: Recombination and Cancer Two forms of recombination contribute to the formation of cancer cells Recombination and Cancer Two forms of recombination contribute to the formation of cancer cells 1. Homologous Recombination Reactions mediated by base pairing between participating DNAs Recombination and Cancer Two forms of recombination contribute to the formation of cancer cells 1. Homologous Recombination Reactions mediated by basepairing between participating DNAs 2. Nonhomologous Recombination Reactions that proceed with little or no basepairing opic I: Homologous Recombination Homologous recombination (HR) is a normal aspect of meiosis. Homologous recombination (HR) is a normal aspect of meiosis. Blocking HR blocks meiosis and leads to sterility. Homologous recombination is also needed for maintenance of genome integrity Breast cancer BRCA2 gene increases HR repair loss of BRCA2 function is common in mammary tumors In mammals RAD51 and DMC1 mediate strand exchange RAD51 KO is lethal DMC1 KO is viable but sterile double strand breaks can initiate homologous recombination homologous recombination Can lead to different outcomes Crossover No crossover Figure 1 Model showing the role of homologous recombination in defending genome integrity during DNA replication Figure 1 Model showing the role of homologous recombination in defending genome integrity during DNA replication Biochemical Society Transactions www.biochemsoctrans.org Biochem. Soc. Trans. (2004) 32, Biochemical Society Transactions www.biochemsoctrans.org Biochem. Soc. Trans. (2004) 32, 957-958 957-958 No crossover Crossover mutations caused by crossing over Mutations caused by homologous recombination + X Unequal cross overs + X deletion Alu elements and human disease Alu elements and human disease 500,000 copies of Alu per genome amplify at rate of 1 insertion per 200 births Alu elements and human disease 500,000 copies of Alu per genome amplify at rate of 1 insertion per 200 births at least 16 genetic diseases are associated with Alu insertion into new locus in a germline cell Alu elements and human disease 500,000 copies of Alu per genome amplify at rate of 1 insertion per 200 births at least 16 genetic diseases are associated with Alu insertion into new locus in a germline cell some cancers are caused by unequal recombination between Alu repeats in a somatic cell AML (acute myelogenous leukemia) Breast cancer (BRCA genes) Alu elements and human disease 500,000 copies of Alu per genome...
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This note was uploaded on 08/17/2009 for the course 26CB 880 taught by Professor Khan during the Spring '07 term at University of Cincinnati.

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cancer2008-3 - Recombination and Cancer Two forms of...

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