Regulation of Cell Division - RR Flashcards
What are the purposes of the cell cycle check points?
to ensure proper duplication, segregation and division, 4 phases G1, S, G2, M, all checkpoints can be blocked by damaged or incompletely replicated DNA
What are the three checkpoints?
Enter S, Enter M, Exit M (Transition from meta to anaphase)
What happens in the Enter S checkpoint? What blocks this checkpoint?
Cell undergoes commitment to proceed through mitosis
Blocked by unfavorable extracellular environment
What happens at the Enter M checkpoint? What blocks this checkpoint?
Cell enters active mitosis
Blocked by DNA damage
What happens at the Exit M checkpoint? What blocks this checkpoint?
transition from metaphase to anaphase
Blocked by improper chromosomal attachment to mitotic spindle
what regulates progression through the cell cycle?
cdk
what is cdk comprised of?
catalytic Kinase
regulatory Cyclin
which portion of cdk is constitutive and which has a concentration that fluctuates
kinase is constantly present, cyclin gets synthesized and proteolyzed in cycles
How is CDK activated?
- Addition of inhibitory phosphate to kinase via Wee1
- Addition of activating phosphate to the kinase via Cak
- Removal of inhibitory phosphate off kinase via protein phosphatase
How is CDK inactivated?
Cyclin gets ubiquinated by an E3 ubiquitin ligase, targeting the cyclin for proteolysis
What is APC
Anaphase Promoting Complex - its the E3 ubiquitin ligase controlling checkpoint Exit M
How does APC work
When all kinetochores are under tension, APC signals degradation of sequestering protein Securin, so that Separase is free to cleave the cohesion complexes
What does activation of p53 pathway result in
apoptosis or cell cycle arrest
how is p53 activated
it is phosphorylated
what is the p53 mechanism of action
once activated (phosphorylated), p53 binds to the regulatory region of the p21 gene. p21 is a cdk inhibitor protein, thus, once synthesized, it blocks the cell form entering S phase
