BIOL 4010 Lecture Notes - Microsatellite Instability, Anaphase-Promoting Complex, Spindle Checkpoint
28 Nov 2013
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Document Summary
One of the key enzymes involved in genomic stability and recruitments of repair proteins is parp ( poly adp-ribose polymerase 1) If dna damage area parp is recruited and makes huge chains of polymerized. Adp ribose tail allowing binding of other repair enzymes to fix the dna. Used in chemotherapy via inhibition of this parp enzyme. In most cells when parp is inhibited then its compensated by homologous recombination : important for brca1 and brca2 derived cancers where recombination is inhibited naturally in the cancer. Synthetic lethality: many gene defects leading to cell death. If we cause enough damage in cancer cells then the cell can die if specific pathways are knocked out example : brca2 mutants are extremely sensitive to parp inhibitors ( known as. Misfiring of mechanisms for rearranging immunoglobulin ex: bcr-abl & myc. Breakage-fusion cycles at crisis when telomeres are critically short ex: p53 mutation. ** there is a disequilibrium in every chromosome in cancer cells.
