What are the three major regulation steps in the cell cycle?
G1-S (commitment step to enter mitosis); G2-M (entry into mitosis); (exiting M, going from metaphase to anaphase in mitosis)
What is the enzyme that has high activity during mitosis? What does it need to be coupled with? How does the second thing's concentration change?
Cdk (cyclin-dependent kinase); needs cyclin; concentration fluctuates from being low near end of mitosis and rising during interphase until new mitosis
How many phosphates are needed with cdk regulation? What removes one of these phosphates? What puts them on? What does removal of the phosphate help promote?
2 (one activating, the other inhibitory); activating phosphatase (Cdc 25); inhibitory kinase (Wee1) and activating kinase (Cak); positive feedback where more active Cdk molecules are made
How can Cdk be shut down (2 ways)?
Use E3 ubiquitin ligase (targets cyclin subunit for proteolytic destruction by proteosome); phosphatase removes activating phosphate
What is the name of the E3 ubiquitin ligase that shuts off mitotic Cdk? What is its other function?
Anaphase promoting complex (APC): turns off Cdk activity and promotes chromosome separation by activating protease Separase
What is the trigger for the metaphase to anaphase transition? What blocks this transition?
Tension on all the kinetochores; if one chromosome fails to attach to both poles
How many cyclins/cdks are needed in the cell cycle?
Different cyclins and cdks present at each cycle stage
How can you turn off different cdks at any point given there are overlapping patterns of activity?
Specificity of inactivation comes from tareting of specific cyclins by different E3 ubiquitin ligases
With DNA damage, what is activated? What does this active product bind to and do?
Protein kinases that phosphorylate p53; binds to p21 gene and leads to p21 (cdk inhibitor protein) made to allow for damage repair or signal apoptosis
What is involved in DNA DSB repair? What can aid with SSB repair? What is another way to increase rate of apoptosis besides inhibiting SSB repair system?
BRCA1 and BRCA2; PARP; Use cisplatin, which is a DNA damaging agent
How can cell cycle be externally controlled?
Growth factors can help increase rate of protein synthesis and other metabolic processes while also decreasing protein degradation rate to allow cells to hit critical growth status
What does activation of the G1 CDK mean? What can activate G1 CDK?
Inactivates retinoblastoma protein and triggers gene synthesis needed to enter S phase; mitogens using receptor tyrosine kinases that activate MAPK pathway