L: Cell Division

complete - could add more detail from diagrams

What are essential features of cell division?

Faithfully replicating genetic material and accurately segregate into daughter cells

What occurs in the M phase?

Mitosis (nuclear division) and cytokinesis (cytoplasmic division)

What is another name for nuclear division?

Mitosis

What is another name for cytoplasmic division?

Cytokinesis

What is the M phase critically controlled by?

Cyclin dependent kinases

How can you describe the activity of cyclin dependent kinases?

It is cyclical

When is cyclin dependent kinase active?

When it is bound to its cofactor

What is the cofactor of cyclin dependent kinase?

Cyclin

What regulates the activity of cyclin dependent kinases?

Phosphorylation and dephosphorylation

which cell divisions do cdk complexes control events in?

Every cell division

Is the cdk used in each stage of the cell cycle the same?

No

What process leads to the destruction of cdks?

ubiquitination of cyclin (→ destruction of cyclin)

Why are accumulation and destruction of cdks important?

It allows the cell cycle to continue in one direction and prevents DNA replication and mitosis occurring more than once in a cycle

Which part of the ubiquitin-cyclin complex does the proteasome recognise?

Polyubiquitin part

What are checkpoints?

Ways of stopping the cell cycle

What checkpoint occurs in the G1 phase?

Check for DNA damage

What checkpoint occurs in the G1-S phase?

Unfavourable extracellular environment

What check point occurs in the end of S phase?

Check for damaged or incompletely replicated DNA

What checkpoint occurs in G2?

Check for damaged or incompletely replicated DNA

What checkpoint occurs in M phase?

Check for chromosome improperly attached to mitotic spindle

What can happen if conditions are not right for cell division?

transcription of inhibitors

What inhibits cdks?

Cyclin dependent kinase inhibitors

What do cdk inhibitors do?

Convert active cdk into inactive cdk

What is p21?

A cdk inhibitor protein

What is needed for full activation of cdk?

Cdk activation kinase

What is the G1/S transition also known as?

R-point

What is Rb?

An key protein for regulating if a cell can divide

What does the G in G1 and G2 stand for?

Gap - not much happens in these stages (checking stages)

Defects in what genes underlie many tumours?

Genes required to pass the R-point

What does response to DNA damage depend on?

The stage of the cell cycle

What does p53 do?

Directs transcription of cdk inhibitors

What is the most commonly mutated gene in human cancers?

Gene which encodes the P53 protein

What does CHK2 activation result in?

inhibition of key cell proteins like cdc25 and arrest of the cell cycle

What triggers the activation of CHK2?

DNA damage

Is regulation of formation of the spindle tight or relaxed?

Tight

What stage does breakdown of the nuclear envelope occur?

Prometaphase (phosphorylation of nuclear lamins)

What is the role of cdks in nuclear envelope breakdown?

Makes sure the nuclear envelope doesn’t break down too early

Which checkpoint checks the attachment of chromosomes?

Metaphase checkpoint

What two things does the metaphase checkpoint check?

The attachment of chromosomes and also that they are attached to spindles from the opposite pole

What is the requirement during metaphase for mitosis to proceed?

Chromosomes are properly attached and under tension

What does the cohesion complex hold together?

Sister chromatids - until they are ready to divide

What defects can cause Robert’s syndrome?

Defects in cohesion

What is the ratio of Roberts syndrome?

37:46870

What does APC stand for?

Anaphase promoting complex

What is APC?

E3 ubiquitin complex

What is the role of active separase?

Cuts cohesion complex, allowing chromosomes to move to opposite poles of the cell

What inhibitory protein binds with and regulates separase?

Securin

Why is it important that separate activity is tightly controlled?

So that the chromosomes are not separated too early

What is aneuploidy?

Abnormal number of chromosomes present in a cell

What checkpoint defect can result in anueploidy?

Defects at the spindle checkpoint

What type of cells can be aneuploid?

tumour cells

What is an example of an anti-mitotic drug?

taxol - it affects the ability of microtubules to depolymerise

What do anti mitotic drugs cause?

Causes unproductive division and the daughter cells to die (cancer treatment)

The degradation of what is essential for mitotic exit?

Cyclins and securin

What are inter polar microtubules?

A structure that appears between separating daughter cells during cytokinesis

What is the contractile ring?

Generates force to split the parent cell into two daughter cells (myosin and actin)