Question

DNA polymerase can sometimes make mistakes. When this is detected the cell cycle halts and works on repairing the mistakes. List two genes that, when their function is lost, would not allow cells to halt their cell cycle. Please explain in a sentence or two why the loss of function mutations in each gene would have this effect.?

Answer 1

Tumor suppressor genes are genes that encode proteins that stop cell cycle and prevent the proliferation of cells. Normally this is in response to some fault, in DNA or other cell cycle mechanisms found at the cell cycle checkpoints.   If these tumor suppressors have a loss of function mutations, then they would not be able to stop the cells from proliferating and this could lead to cancer.

Retinoblastoma (Rb) is a tumor suppressor that plays a crucial role in the G1 checkpoint which prevents the cells from entering the S phase, by binding to the transactivation domain of E2F,  if any error in the cell cycle is found. loss of function mutations in Rb would lead to the protein not being able to bind to the DNA and so the cell cycle progress cannot be halted. This loss of function of Rb has been found in people with the tumor of retina, i.e. retinoblastoma and this was the first tumor suppressor to be discovered.

p53 is a 53kDa protein that acts as a major tumor suppressor molecule and has been found to be having loss of function mutations in multiple cancers.p53 reacts to cellular stress signals such as increased reactive oxygen species levels, detaches from Mdm2 and becomes active, binds to DNA as a tetramer ( binding of p53 to DNA shows positive cooperativity with the binding of each monomer increasing the affinity for binding of the other monomers to form the tetramer) and induces specific responses such as apoptosis. So a loss of function mutation of p53 would impair apoptotic signaling and so cell cycle arrest and apoptosis do not take place and the cell continues to proliferate.