Exam 2 10/11 Britton Flashcards
What is the cell cycle
Set of 4 phases in which DNA/cellular components duplicate and divide into daughter cells
What are the phases of the eukaryotic cell cycle
- G1
- S phase
- G2
- M phase
Interphase is made up of:
G1, S phase, G2
G1 phase
cell grows and synthesizes all cellular components that are essential for DNA duplication
S phase
DNA synthesis replicates the genetic material
(each chromosome duplicated/2 sister chromatids)
G2 phase
Cell prepares for division in M phase
M phase
Mitosis/cytokinesis - generates 2 identical daughter cells
What are the cell cycle checkpoints?
Regulate cell cycle transition
- G1 checkpoint
- G2 checkpoint
- M checkpoint
G1 checkpoint
determines whether conditions are favorable for cell division to proceed
G2 checkpoint
correct chromosome duplication is assessed
M checkpoint
attachment of each centromere to the spindle fibers is assessed, mitosis only proceeds if this is correct
At each cell cycle checkpoint, cell examines:
internal and external cues and decides whether or not to move forward with division
Cell enters next phase of division if:
Necessary conditions exist
Cell cycle is halted if:
Necessary conditions are not met
Normal cells transition through the cell cycle in a ____ way
Regulated
Cell division, growth, repair of genetic damage is regulated
Errors in checkpoints have _____
Catastrophic consequences - uncontrolled cell division or cell death
Regulation of the cell cycle involves what proteins/enzymes?
- cyclins
- cyclin dependent kinases (CDK)
____ are serine/threonine protein kinase enzymes that phosphorylate specific target proteins
CDKs
____ act as the signal for the cell to pass into the next phase of division
CDKs
CDKs are inactive in the absence of
Cyclins (cyclins bind to CDKs and activate them)
____ are regulatory proteins with no catalytic activity
Cyclins
True or false: Cyclins themselves have catalytic activity
False
After binding to CDKs, what eventually happens to cyclins?
Get degraded by cytoplasmic enzymes, deactivating the CDKs
Cyclin-CDK complexes are unique to:
Each cell cycle phase
Cyclin-CDK complexes activate:
Specific genes to drive cells through the cell cycle
Cyclin A can form a complex with which CDK(s)?
CDK 1 and CDK 2
Which phase of cell cycle is associated with CDK1 and Cyclin A/B complexes?
Mitosis
Cyclin E can form a complex with which CDK?
CDK 2
Which phase of cell cycle is associated with CDK2 and Cyclin A/E complexes?
Entry into S phase
Cyclin D can form complexes with which CDK?
CDK 4 and 6
Entry into G1 phase requires which cyclin/CDK complexes?
CDK4-cyclin D
CDK6-cyclin D
Cyclins and CDKs must undergo _____ during the cell cycle
constant cycle of synthesis and degradation
Before a cell can progress from one phase of the cell cycle to the next:
it must degrade the cyclin that characterizes that phase of the cell cycle
If cyclin is not degraded:
Cell cycle does not continue
Favorable conditions for replication
- growth factor signals
- DNA integrity
- cell size
- protein reserves assessed
What checkpoint is referred to as the restriction point?
G1
What happens at the restriction point?
Cell is committed to division and moves into the S phase
If conditions are not favorable during G1 checkpoint:
cell enters G0 resting state, await further signals when conditions improve
True or false: some cells remain in G0 for lifetime
True - neurons, skeletal muscle cells
Transition from G1 to S phase is ruled by: (2)
- CDK4/6-cyclin D (G1 checkpoint)
- CDK2-cyclin E (entry into S phase)
What is E2F
transcription factor important for cell growth
What happens when E2F is bound to retinoblastoma (Rb) protein?
Production of proteins necessary for G1/S transition is blocked
Rb
Retinoblastoma protein
tumor-suppressor protein/negative regulator of cell cycle
How does E2F get released from Rb?
CDK4/6-CyclinD phosphorylates Rb, releasing E2F
E2F induces ____ progression in association with ____
S-phase; CDK2-cyclin E
Ras protein is a
Proto-oncogene
Ras activates:
G1 checkpoint cyclins
What happens if Ras protein is mutated?
- Becomes constantly active so will constantly activate G1 cyclins, leading to uncontrolled cell cycle into S phase
- causes cancer
____ checkpoint prevents entry into M phase if certain conditions are not met
G2
What happens if DNA is not properly replicated/intact during S phase?
- Cell cycle is paused at G2 checkpoint
- cell will attempt to complete DNA replication or repair the damaged DNA
Forkhead box M1 protein
transcription factor that allows for transition to M phase
activates expression of FoxM1 target genes
In order for FoxM1 to become active, what needs to happen?
Needs to get phosphorylated by CDK2-cyclin A and CDK2-cyclin E
M checkpoint also known as
Spindle checkpoint
What are the mitotic CDK’s?
CDK1-cycin A, CDK1-cyclin B
G1/S phase CDKs are inhibited by
Mitotic CDKs
When mitotic CDKs are high during M phase, what happens?
factors that initiate DNA replication are inhibited
2nd DNA synthesis stopped til mitosis is complete/passes G1 checkpoint
Mitotic CDKs activate:
APC/C
APC/C function
allow chromatids to separate at anaphase and complete mitosis
___ decreases the possibility to aneuploidy
APC/C
Negative regulators of the cell cycle- function
Halt the cell cycle