You are carrying out experiments designed to ascertain the defect in a cell line derived from a breast cancer tumor. Your studies show that these cells likely arose due to an inability to control progress through the cell cycle in the presence of DNA damage. Exposure of the cells to a dose of γ-irradiation results in a significant propagation of mutated nucleotides into the DNA of daughter cells. Given these observations, which of the following proteins/complexes is most likely defective in your study cell line?
A) anaphase-promoting complex
B) CDK4/6
C) cohesin
D) p53
E) pRB

Question

Quizplus · Accepted Answer

One major function of the p53 protein is to serve as a component of the checkpoint that controls whether cells enter as well as progress through S-phase. The action of p53 is induced in response to DNA damage. Under normal circumstances p53 levels remain very low due to its interaction with a member of the ubiquitin ligase family called MDM2. In response to DNA damage, for instance, as a result of UV-irradiation or γ-irradiation, cells activate several kinases including checkpoint kinase 2 (CHK2) and ataxia telangiectasia mutated (ATM). One target of these kinases is p53. ATM also phosphorylates MDM2. When p53 is phosphorylated it is released from MDM2 and can carry out its transcriptional activation functions. One target of p53 is the cyclin inhibitor p21Cip1 gene. Activation of p21Cip1 leads to increased inhibition of the cyclin D1-CDK4 and cyclin E-CDK2 complexes, thereby halting progression through the cell cycle either prior to S-phase entry or during S-phase.

You Are Carrying Out Experiments Designed to Ascertain the Defect