Tumor Suppressor Genes and Oncogenes
enzymes that repair DNA
BRCA1, BRCA2, ATM
p53
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
retinoblastoma
acts at the G1/S checkpoint to downregulate the cell cycle
differences between tumor suppressor genes and oncogenes
both are normal genes of the cell cycle, but tumor suppressor genes act as the "brakes" and oncogenes act as the "gas pedal"
role of tumor suppressor genes in cancer
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
tumor suppressor genes
genes that control the cell cycle, apoptosis,DNA repair
gene dosage effect
half the normal amount of protein isn't enough for normal cell processes can lead to haploinsufficiency
role of oncogenes in cancer
must be constituently activated: -amplification -mutation -overproduction of stimulatory molecules all leads to unregulated growth
proto-oncogenes
normal cellular genes that regulate cell growth and differentiation must be abnormally activated into oncogenes to promote tumor growth
dominant negative effect
occurs when the abnormal, mutated protein blocks the function of the normal protein that is still being produced can lead to haploinsufficiency
function of tumor suppressor genes
prevent or suppress cancer in active form
2 examples of tumor suppressor genes
retinoblastoma p53
haploinsufficiency
when the inactivation of one copy of the tumor suppressor gene is sufficient for tumor growth