Topic 7 - Cell cycle Flashcards
If conditions for growth are unfavourable, what can happen to stall the cell cycle?
Cell can stay in one of the G phases for a long time until conditions improve
DNA replication occurs during this phase of the cell cycle
S phase
Why is yeast a great model system to study the cell cycle?
- Replicates fast
- Small and easy to cultivate
- Easy to genetically manipulate
- Can be haploid
What is advantageous about working with early stage embryos?
Because the cells don’t grow much in very early phases, the cell cycle is periodically “condensed”
In addition to sorting cells, FACS can be used to…
Determine which cells are in what phase of the cell cycle
What are 3 properties of the cell cycle control system?
- Binary - yes or no
- Irreversible, once u enter u cannot leave
- Highly adaptable and can be modified
If Cdks are always present in the environment, why is only one Cdk active at a time?
Depends on activation by cyclin and whether or not inhibitory phosphate is present
What are the 2 functions of cyclin?
- Activate Cdks
2. Direct Cdks to target proteins - specify the Cdk’s functions
During which part of the cell cycle does the APC/C start to control the cell cycle?
Partway through M-phase (mitosis) - promotes anaphase
APC/C catalyzes the (process) of two main proteins
- Ubiquitylation/ubiquitination
2. Securin and S and M-cyclins
What protein binds to an inactive APC/C to activate it?
Cdc20
Describe the action of APC/C in anaphase
Degrades securin which is normally bound to separase, when securin is degraded separase is activated and it cuts the cohesin proteins which attach sister chromatids together during metaphase
Cyclins rise in the cell cycle during…
Late G1 phase until partway through M-phase
How do Cdks exert effects on target proteins?
Dephosphorylate them
What is a CKI?
A Cdk inhibitor protein
What is a key step in the transition of Cdk > APC/C control of the cell cycle?
All that was phosphorylated by Cdks will be dephosphorylated
Proteolysis (i.e. the breakdown of securin and Cdks) are controlled by this complex
SCF complex (Skp1, cullin, F-box protein)
What are the components of the SCF complex?
Skp1
Cullin
F-box protein
Activation of the SCF complex happens when you want cyclins to be (active/inactive)
Active: they degrade CKIs (cdk inhibitors)
The F-box of the SCF complex only recognizes proteins to be ubiquitylated if they are…
Phosphorylated
Recognizing DNA damage will arrest the function of these cyclins in the cell cycle
G1/S-Cdk, S-Cdk, M-Cdk (All of them!)
Unreplicated DNA will arrest the function of these cyclins
M-Cdk
If the chromosome is unattached to the mitotic spindle, what cell cycle control protein will be inhibited?
APC/C
To make sure the cell is in good condition to enter the cell cycle, the cell recognizes signals from the (intracellular/extracellular) environment
Both!
M-Cdk inhibits this process
DNA rereplication
How does Cdc25 activate Cdks?
Removes their inhibitory phosphate group
Are the Cdk and APC/C systems ever active at the same time?
Never
What aspects of accuracy are required when a cell is in the S-phase?
- No mistakes
2. Replicated only once - no rereplication
Describe the prereplicative and preinitiation complexes of S-phase
Prereplicative: the protein complexes present while DNA is not being replicated - machinery is ready to go but DNA replication has not been initiated
Preinitiation: DNA helicase activated, accessory proteins at the ready for DNA to be transcribed
The prereplicative complex of G1-phase is stimulated by…
APC/C - no DNA replication
The preinitiation complex of S-phase is activated by…
S-Cdk
The prereplicative complex of the G1 phase is inhibited by…
Cdk activity
The role of helicase is to…
Unwind DNA
DNA replication starts at…
Origin recognition complexes
When is the origin recognition complex present on the DNA during the cell cycle?
Present the whole cycle
How is the preinitiation complex activated?
Cdc6 associates with the origin recognition complex
Active helicase is also bound to…
Cdt1
Association of the prereplicative complex occurs when…
Cdt1 dissociates from helicase and Cdc6 dissociates from the ORC using ATP hydrolysis. This dissociation causes the recruitment of 2 helicases (forming the prereplicative complex)
What enzyme activates helicase by phosphorylating it?
DDK
How does S-Cdk contribute to the “activation” of the prereplication complex?
Phosphorylates initiator proteins which associate with DNA helicase and cause dissociation of the ORC complex
Describe the recycling of the ORC machinery
There is no recycling! When it is all activated, it is phosphorylated and then when it dissociates it is dephosphorylated and degraded
i.e. ONLY USED ONCE
When inactive and not associated to DNA, helicase and Cdt1 are also bound to…
Geminin
What is geminin?
An inhibitor of Cdt1
