The p53 and MDM2 proteins are involved in the DNA damage response pathway (figure 1). In the absence of DNA damage, MDM2 mediates the degradation of p53. In the presence of DNA damage, p53 is not broken
down and forms active tetramers that stimulate the expression of genes that block cell cycle progression.
Red blood cells are produced by the division and differentiation of multipotent stem cells. Researchers have
observed that mice with a partial loss-of-function mutation in the MDM2 gene have a lower concentration of red
blood cells in the blood than do mice that express the wild-type MDM2 allele.
(a) Using the model of the p53/MDM2 pathway, connect the reduction of MDM2 function in mutant mice to
the observed concentration of red blood cells.
(b) Predict how a loss-of-function mutation in the p53 gene is most likely to affect the cell cycle in response to
DNA damage. Justify your predictions.