Cell Cycle Worksheet Flashcards
What are the phases of the cell cycle? What is the average length of the mammalian cell cycle? What are some exceptions?
G1, S, G2, M; 18-24 hours; early embryos
When do cells become committed to progression through the cell cycle? What is the mechanism that regulates this step?
when they pass R; external growth factors
How is progression through the cell cycle connected to changes in the cells environment? Why must cells complete the cell cycle once they are committed to progression?
based upon presence or absence of growth factors; DNA is being replicated
What is the mechanism by which the cell replicates its DNA once and only once?
phosphorylation of the ORC and by binding of the MCM helicase to the replication origins
What external signals regulate the cell cycle? What is their mechanism of action?
nutrients or growth factors; GFs bind to their receptors to begin the cascade through Ras/Raf/Mek/Erk, causes synthesis of Cyclin D which forms complexes w/ Cdk4,6; if GF withdrawn, Cyclin D quickly degraded –> G0; if GF remains present, or cell past R, cell enters S and commits to division
What internal signals link the external signals to the events of the cell cycle? What are the quality control checks on the cell cycle? What is the mechanism of the DNA damage checkpoint?
cyclins and cdk’s; checkpoints w/in G1, S, and G2; ATM and ATR find ds and ss breaks (respectively) –> add P to Chk1 or Chk2 –> add P to cdc25 phosphatase –> inhibits act. of Cdk1 and Cdk2 by cdc25 not removing P of Tyr 15…. ATM and Chk2 also add P to TF p53 –> incr. synthesis of P21 –> inhibits Cdk2/Cyclin E –> inhibits entering S
What is MPF?
What are CDKs?
What are cyclins?
> complex of Cyclin B and Cdk1
group of protein kinases that are activated by formation of a complex w/ a cyclin and are involved in the regulation of the cell cycle
proteins that are associated with the cell cycle that initiate certain processes in the cell cycle
When are specific pairs of cyclins and CDKs active in the cell cycle?
Cdk 4,6 and Cyclin D: early G1 through R Cdk 2 and Cyclin E: G1 to S transition Cdk 2 and Cyclin A: S Cdk 1 and Cyclin A: S to G2 transition Cdk 1 and Cyclin B: G2 to M transition
What is the mechanism by which the activity of CDKs is regulated?
(use Cdk1 and Cyclin B)
CAK adds P to Thr 161 and wee1 kinase adds P to Tyr 15 of Cdk1, the Tyr 15 P inhibits Cdk1 until stimulus received; stimulus–> cdc25 phosphatase removes P from Tyr 15 –> act. MPF –> adds P to target proteins; Cyclin B later destroyed by proteasome, which inact. Cdk1; Cdk1 farther inact. by removing P from Thr 161
What are CDK inhibitors?
Ink4: p15, p16, p18, and p19; binds Cdk4,6, inhibiting progression through G1
CIP/KIP: p21, p27, and p57; binds Cdk2/Cyclin A or Cdk2/Cyclin E and inhibits progression through G1 and S phases
Describe how the CKI p27 plays a role in the regulation of the cell cycle.
CKI p27 inhibits Cdk2/Cyclin E in early G1; inhibition relieved by increased synthesis of Cyclin E and inactivation of p27 by its binding to Cdk4,6/Cyclin D and its degradation; activation of Cdk2/Cyclin allows cell to pass R and move into S phase
What are the consequences of errors in cellular replication?
mutations, aneuploidy, and possibly cancer
