The following is the regulatory network that controls the activity of the mitotic regulatory kinase (Cdk-1) that is critical for the G2→M phase transition of a cell during the cell cycle. • DNA damage or failure to complete DNA replication results inactivation of p53.
• The activated p53 regulates Cdk1/ Cyclin B function byinhibiting PIK1.
• PIK1 normally inhibits Myt1/ Wee1 kinase and activatesCDC25.
• The Myt1/Wee1 kinase normally inactivates Cdk1 whereasCDC25 activates Cdk1.
• The Cdk1-CyclinB is active when dephosphorylated andinactive when phosphorylated.
a) The mutations in proto-oncogenes that contribute to unlimited cell division are dominant, gain-of function (GOF) mutations as opposed to the mutations in tumor suppressor genes, which arerecessive, homozygous, loss-of-function (LOF) mutations. Which of the proteins are encoded by….
i. Proto-oncogenes:
ii. Tumor suppressor genes:
b) In a diploid yeast undergoing the cell cycle, you identify a Cyclin B (or M-Cyclin), which functions at the G2->M transition. A temperature sensitive Cyclin B mutant fails to complete cell cycle at 42°C since it arrests the cell at a particular cell cycle phase. Give the ploidy of the arrested cell:
c) Would a PIK1 temperature sensitive mutant, grown at the non-permissive temperature (42°C), progress from G2→M phase? Why or why not?
d) Cisplatin is a chemotherapeutic drug that disrupts DNA replication and thus activates the DNA damage checkpoint such as p53. How would the activation of this checkpoint disrupt tumor growth?
e) Circle the amino acid that can be phosphorylated by the Cyclin D-CDK complex.   

DNA CDC25 damage Cdk1 Cdk1 PIK1-p53 Cyclin B-P (inactive) 1 Cyclin B Myt1/ Weel (Active)