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