genes that control the cell cycle, apoptosis,DNA repair
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function of tumor suppressor genes
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prevent or suppress cancer in active form
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haploinsufficiency
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when the inactivation of one copy of the tumor suppressor gene is sufficient for tumor growth
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gene dosage effect
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half the normal amount of protein isn't enough for normal cell processes
can lead to haploinsufficiency
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dominant negative effect
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occurs when the abnormal, mutated protein blocks the function of the normal protein that is still being produced
can lead to haploinsufficiency
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p53
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DNA-binding protein that regulates transcription of numerous genes
plays critical role in cell-cycle arrest and induction of apoptosis in presence of DNA damage
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2 examples of tumor suppressor genes
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retinoblastoma
p53
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retinoblastoma
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acts at the G1/S checkpoint to downregulate the cell cycle
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proto-oncogenes
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normal cellular genes that regulate cell growth and differentiation
must be abnormally activated into oncogenes to promote tumor growth
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differences between tumor suppressor genes and oncogenes
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both are normal genes of the cell cycle, but tumor suppressor genes act as the "brakes" and oncogenes act as the "gas pedal"
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role of tumor suppressor genes in cancer
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frequently targeted by cancer --> can be deleted or inactivated by methylation to either 1 allele or both --> keeps genes from stopping cell growth
ex. p53 is upregulated in presence of DNA damage to arrest cell cycle and have DNA repair
RB is hyperphosphorylated --> RB inactivated --> cell goes through G1/S checkpoint --> uncontrolled growth
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role of oncogenes in cancer
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must be constituently activated:
-amplification
-mutation
-overproduction of stimulatory molecules
all leads to unregulated growth
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enzymes that repair DNA
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BRCA1, BRCA2, ATM
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