The Cell Cycle Flashcards by Tori Whalen

The cell cycle consists of (2)

Mitotic (M) phase (mitosis and cytokinesis)
Interphase (cell growth and copying of chromosomes in
preparation for cell division)

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Interphase (about 90% of the cell cycle) can be divided into subphases:

G1 phase: first gap
S phase: synthesis
G2 phase: second gap
G0 phase: resting phase, postmitotic quiescent

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the first gap phase

G1 phase: first gap

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Preparatory growth phase prior to cell entering DNA synthesis phase

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what cells are metabolically active during G1

Requires nutrients & growth factors
RNA, protein, lipid and carbohydrate synthesis occurs

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Duration of G1. It is ____ in embryonic and cancer cells and __________ in rapidly dividing cells

Duration: variable (6-24hrs)
short and Rapid or non-existent

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where DNA and chromosomal protein
synthesis occurs

Phase s

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Duration of S phase

lasts approximately 7-8 hours in a typical mammalian cell with
a 16 hour cycle

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In S phase, __________ are no longer needed. __________ occurs here, creating
two identical ______________

Growth factors no longer needed

DNA replication occurs here, creating two identical daughter genomes

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what is second growth phase

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Interval between DNA synthesis (S phase)
and mitosis (M phase)

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synthesize of what occurs during G2 phase. Does cell growth continue?

enzyme, protein and ATP synthesis occur

yes, cell growth continues

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Duration of G2

lasts approximately 3 hours in a typical mammalian cell with a 16-hour cycle

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what is the mitotic phase where the cell undergoes mitosis and then cytokinesis?
What is the duration of this phase?

Mitotic phase
Duration: 1-2 hours

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State of withdrawal from cell cycle. Cell is neither dividing nor preparing to divide

G0 phase

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in what phase, is the cell described to be “doing its job” - performing its function within the tissue

G0 phase

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Examples of cells in G0:

Hepatocytes, neurons

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Checkpoints are based on a series of biochemical switches to initiate specific cell-cycle events.

cell cycle control system

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Checkpoints are based on a series of ______________ to initiate specific cell-cycle events.

biochemical switches

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Feature of the biochemical switches: Generally ______ (on/off) to launch an event in a complete & irreversible fashion

binary

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what are the 3 features of biochemical switches?

they are binary
they are robust and reliable
they are adaptable and modified to suit specific cell types

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where are modifications to the cell cycle control system usually seen?

Cyclin dependent kinases (Cdks)

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Points in the eukaryotic cell division cycle where progress through the cycle can be halted until conditions are suitable for the cell to proceed to the next stage

Checkpoints aka “Transitions”

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Checkpoints can be regulated by:

Factors within the cell, mostly controlled by the “health” or “state of preparation” of the cell
Factors from outside the cell – i.e. messages from other cells within the same tissue or distant cells

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Three major regulatory transitions at the:

1. Start Transition (aka G1/S) 2. G2/M transition 3. Metaphase-to-anaphase transition (aka M-to-A)

For most cells, the ____ seems to be the rate-limiting and committing step of the cell cycle

G1/S at every stage after this, the cell will either have to divide or it will die

what checkpoint would you ask: is the environment favourable?

G1/S

what checkpoint would you ask: is all the DNA replication? Is the environment favourable?

G2/M transition

what checkpoint would you ask: are all the chromosomes attached to the spindle?

Metaphase-to-anaphase transition (aka M-to-A)

Cdks are controlled a group of proteins called

cyclins

There are 4 classes of cyclins that form specific complexes with Cdks

1. G1 cyclins: Cyclin D 2. G1/S cyclins: Cyclin E 3. S-cyclins: Cyclin A 4. M cyclins: Cyclin B

Forms complex with Cdk4 or Cdk 6 Involved in G1 phase of cell cycle, needed for initiation of transcription of G1/S cyclins to help promote passage through start transition

G1 cyclins: Cyclin D

Cdks are responsible for cyclical changes in _______________ of intracellular proteins that initiate/ regulate the major events of the cell cycle

phosphorylation

Cyclical changes in cyclin protein levels result in the cyclic assembly and activation of ________________ at specific stages of the cell cycle.

cyclin–Cdk complexes

* Forms complex with Cdk2 * Bind Cdk’s at the end of G1 & help trigger progression through start transition * Levels decrease in S phase

G1/S cyclins: Cyclin E

* Forms complex with Cdk1 and Cdk2 * Bind Cdks after progression through start transition & helps stimulate chromosome duplication during S phase * Levels remain elevated until mitosis; contributes to control of some early mitotic events

S-cyclins: Cyclin A

* Forms complex with Cdk1 * Bind CdKs to stimulate entry into mitosis at the G2/M transition * Levels decrease in mid-mitosis

M cyclins: Cyclin B

Cyclin D and CDK 4 and 6 create which cyclin-cdk complex?

G1-CDK

Cyclin E and CDK 2 create which cyclin-cdk complex?

G1/S-CDK

Cyclin A and CDK 2 and 1 create which cyclin-cdk complex?

S-CDK

cyclin B and CDK 1 create which cyclin-cdk complex?

M-CDK

which cyclin-cdk complex is needed for progression through the start transition. What is it made up of?

G1-CDK - Cyclin D, CDK 4, and CDK6

which cyclin-cdk complex is needed to trigger progression through the start transistion. What is it made up of?

G1/S-CDK made up of Cyclin E and Cdk 2

which cyclin-cdk complex is to stimulate chromosome duplication and is involved in early mitotic events? What is it made up of?

S-CDK made up of the Cyclin A, CDK2 and CDK1

which cyclin-cdk complex is needed to stimulate progression through the G2/M checkpoint. What is it made up of?

M-CDK is made up of cyclin B and cdk 1

How do cyclin-Cdk complexes work?

Cyclins function by activating (phosphorylating) the Cdk Cyclin protein does not simply activate its Cdk partner, but also directs it to a specific target protein

Progression through the _____________ checkpoint is a little different

Metaphase-to-anaphase

the anaphase promoting complex (APC) is a member of what ligase family of enzymes

ubiquitin

What is APC used for?

to stimulate proteolytic destruction of specific regulatory proteins

What proteins do APC target for destruction?

securin, M-cyclins, S-cyclins

how does a Metaphase-to-anaphase checkpoint occur?

Occurs via regulated proteolysis

what happens when you ubiquitin something?

You target it for destruction Ubiquitin is used to stimulate the proteolytic destruction of specific regulatory proteins

Early response genes are usually

usually transcription factors

Delayed response gene are usually

usually Cdks, cyclins, or other proteins needed for cell division

G1/S checkpoint: Active G1-cdk (and G1/S-cdk) complex will target a protein called ___ and phosphorylate it

RB functions as a transcription co-repressor. Hyperphosphorylation of RB will ___________ RB

inactivate RB Inactive RB then releases a transcription factor E2F, allowing transcription to proceed

Progression through G1 is delayed if:

* DNA is damaged by radiation, chemicals, or errors * Absence of nutrients or growth factors * Abnormal cell size

Entry into M is prevented when:

* DNA replication is not complete * Presence of DNA damage * Abnormal cell size

Progression through M-to-A is prevented if

Chromosomes are not properly attached to mitotic spindle

How is the cell cycle paused in unfavourable conditions? Two important molecular mechanisms:

- Cdk inhibitory proteins (CKIs) - Proteins coded by tumour suppressor genes

what molecule is primarily used by cells to govern the activities of G1/Sand S-Cdks early in cell cycle

CKIs Binding of Cdk inhibitory protein (CKI) inactivates cyclin-Cdk complex

CyclinD-cdk4 & CyclinD-cdk5 (G1-cdk complex) are inhibited by

p16

* CyclinE-cdk2 (G1/S-cdk complex) * CyclinA-cdk2 & CyclinA-cdk1 (S-cdk complex) * Cyclin B-cdk1 (M-cdk complex) are all inhibited by

p21

* CyclinA-cdk2 & CyclinA-cdk1 (S-cdk complex) * CyclinE-cdk2 (G1/S-cdk complex) * Cyclin B-cdk1 (M-cdk complex are all inhibited by

p27

p53 and RB are examples of

Tumour suppressor genes

what tumour suppressor gene recognizes and binds damaged DNA

p53 Unstressed cells have lower levels of p53 since it will be bound by a protein called Mdm2 and be degraded

what tumour suppressor gene is generally found in active form (hyperphosphorylated) and can recognize damaged DNA