Control of Eukaryotic Cell Cycle 1 Flashcards
What is the cell cycle?
It is the ordered sequence of events that ensures duplication of the entire genome and equal partitioning of the two copies into two genetically identical daughter cells
What is the main (basic) function of the cell cycle?
To duplicate the vast amounts of DNA in the nucleus which is packaged into chromosomes and then segregate these copies evenly into 2 genetically identical daughter cells
What is the first gap phase called?
G1
What happens in G1?
Cells prepare for DNA replication
What is the second gap phase called?
G2
What happens in G2?
Cells prepare for cell division
What happens during S phase?
Chromosomes are replicated
What happens in M phase?
Cells carry out nuclear and cytoplasmic division
How long does chromosome replication (S phase) take?
10-12 hours
What is cell division dependent on?
Activation and deactivation of cyclin-dependent kinase complexes and the switching between DNA duplication and DNA segregation in all cells
What can occur is unwanted/uncontrolled cell division occurs?
Cancer
What are oncogenes/TS genes?
A gene which in certain circumstances can transform a cell into a tumour cell
What can chromosome segregation errors lead to?
Inaccurate distribution of the genetic material to the daughter cells during cell division
What defects can chromosome segregation errors cause?
Gain/loss of material; gain/loss of entire chromosomes (aneuploidy)
What does a mutation in the Wee1 gene mean?
That yeast cells enter mitosis too early while still too small
Explain biochemical regulation of the eukaryotic cell cycle?
G1 and S phase cells mixed (G1 nucleus started replicating early); Cells in S phase contain a dominant activator of DNA replication; G2 nucleus waited and did not re-replicate its DNA and is resistant to S phase promoting factor; Interphase cell starts to segregate chromosomes early even if replication was incomplete;
Both nuclei enter mitosis synchronously even if replication is incomplete
What are the 3 major checkpoints in the cell cycle?
G1/S Phase checkpoint (Restriction Point); G2/M Phase checkpoint; Metaphase/Anaphase checkpoint
What do checkpoints do?
They render the transition between different cell cycle stages sensitive to the completion of key cellular tasks and to the presence of errors
What does the G1/S checkpoint do?
Determines whether all conditions are favourable for cell division to proceed and checks for DNA damage
What are the requirements for the cell in order for it to progress to the S phase?
It must be the appropriate size and have adequate energy reserves
What happens if the cell does not reach the requirements?
The cell can halt the cycle and attempt to remedy the problematic condition or the cell can advance into the G0 phase and await further signals when conditions improve, or apoptosis can occur is DNA is damaged beyond repair
What does the G2/M do?
It ensures that all of the chromosomes have been accurately replicated without mistakes or damages
What happens if problems are detected?
The cell cycle is halted and the cell attempts to either complete the DNA replication or repair the damaged DNA (if it is not repairable, then apoptosis occurs)
What does the Metaphase/Anaphase checkpoint do?
Checks chromosome correctly aligned and attached to the spindle microtubules
What happens if replicated chromosomes are not correctly segregated in the Metaphase/Anaphase checkpoint?
Aneuploidy
How do cyclins work in the G1 phase?
G1/S-cyclins bind to and activate specific G1/S-phase Cdks to help progression through the restriction point
What do S-cyclins do?
They bind to specific S-phase Cdks soon after progress through the restriction point and help stimulate DNA replication, and help control some early mitotic
What do M-phase cyclin-cdk complexes do?
They are inactive at the start G2 and are activated at the end of G2 and trigger entry into M phase at the G2/M transition
How are cyclins degraded during the cell cycle?
Via protein ubiquitinylation
How are ubiquitin molecules added to other molecules?
By E3 ubiqutin ligases
How are ubiquitin molecules removed from other molecules?
Deubiquitinating enzymes
What is the name of the cell cycle regulator that processes E3 ubiquitin ligase activity?
APC/C
How is Cdk activity regulated during the cell cycle?
Binding to a partner cyclin and by phosphorylation
What happens when kinases are activated?
They transfer phosphate groups from ATP to serine and threonine side chains on target proteins
What is protein phosphorylation?
It is reversible PTM event that is mediated by opposing actions of protein kinases and protein phosphatase
How does protein phosphorylation happen?
It occurs through protein kinases and consits of the addition of a phosphate group (PO4) to the polar R group of amino acids
What does the addition of phosphate group on a protein do?
Modifies the protein from hydrophobic apolar to hydrophilic polar
What does the addition of a phosphate group on an amino acid do?
After an amino acid is phosphorylated, it can bind molecules with other proteins and assemble and detach proteic complexes
Since some cellular phosphate esters are phosphorproteins, how are they formed?
Via catalytic enzyme and ATP, with phosphate anhydride acting as a donor
What is the name of the third protein that is required for full activation of Cdk?
Cdk-activating kinase
What does Cdk-activating kinase do?
It adds a phosphate group to a threonine in the T loop, which enables Cdk to bind to and phosphorylate target proteins
What binds to the active site of the cyclin-Cdk complex?
Target peptides
What does the binding of target peptides to the active site of the cyclin-Cdk complex do?
It ensures that the target Serine/Threonine side chains are correctly positioned with respect to the g phosphate of the bound ATP
What can inhibit the activity of Cyclin-Cdk complexes?
Additional phosphorylation of CDKs on inhibitory sites
What is CDK activity controlled by?
Positive regulation by cyclin protein levels; inhibitory/stimulatory phosphorylation of the CDK subunit
What is able to suppress cyclin-Cdk activity?
The binding of Cdk inhibitors
What is the p27 protein?
A cell cycle inhibitory protein
What is the major function of the p27 protein?
Stop or slow down the cell division cycle
How is the p27 protein able to carry out its major function?
By inhibiting the activity of specific cyclin-Cdk complexes and prevents substrate and ATP binding
What can the p27 protein also be classed as?
A tumour suppressor gene because it is often inactivated or deleted in cancer
Where can Cdk inhibitor proteins bind?
Either directly at the kinase active site (blocking kinase activity by interfering with ATP binding) or near the active site (inhibiting substrate binding)
