18.01.06 Cell cycle, mitosis, meiosis, recombination Flashcards
What are the broad stages of the cell cycle?
Quiescent/senescent state = G0
Interphase = G1, S, G2
Cell division = Meiosis/Mitosis
Cytokinesis
Define mitosis.
Is part of the cell cycle in which chromosomes in the nucleus are separated into two identical sets of chromosomes contained within their own nucleus.
Accounts for approximately 20% of the cell cycle and is divided into stages corresponding to the completion of one set of activities and the start of the next.
Describe G0.
A resting phase where the cell has left the cycle and has stopped dividing.
Describe G1.
9-12 hours
Growth phase during which proteins and RNA are synthesised. Each chromosome exists as a single double stranded helix - at no point is DNA synthesised in this phase.
At the G1 checkpoint - the restriction point - the cell is committed to division and moves into the S phase.
Describe S phase.
6-8 hours
DNA synthesis replicates the genetic material. Each chromosome now consists of two sister chromatids.
Each of the 46 chromosomes is duplicated by the cell.
Describe G2.
Loosely coiled replicated chromosomes
Cell continues to grow. The G2 checkpoint ensures enough cytoplasmic materials necessary for mitosis and cytokinesis.
The cell souble checks the duplicated chromosomes for error, making any needed repairs
What is the function of cell cycle checkpoints?
Regulation of the cell cycle involves processes crucial to the survival of a cell, including the detection and repair of genetic damage as well as the prevention of uncontrolled cell division.
Regulatory pathways that control the order and timing of the cell cycle transitions ensuring critical events are completed with high fidelity.
What types of protein regulat the cell cycle?
The cell cycle is regulated by heterodimeric protein kinases composed of:
1) Cyclins - form the regulatory sybunit and have no catalytic activity
2) Cyclin-dependent kinases (CDKs) - inactive in the absence of a partner cyclin. Becomes the catalytic subunit of an activated heterodimer which phosphorylates target proteins to orchestrate coordinated entry into the next phase of the cell cycle.
What is the difference in expression between CDKs and cyclins?
CDKs are constitutively expressed whereas Cyclins are synthesised at specific stages in response to various external stimuli / molecular signals.
What are the three main cell cycle checkpoints?
1) G1/S (restriction) checkpoint
2) G2/M checpoint
3) Metaphase/Spindle checkpoint
What occurs at the G1/S (restriction) checkpoint?
1) Cell growth enables foramtion of the CDC-cycling D
2) Phosphorylated retinoblastima protein
3) Relieves inhibition of E2F transcription factor
4) Cyclin E now expressed, binds to CDK2
5) Allows G1-S phase transition
What occurs during the G2/M checkpoint?
1) CSK1 is activated by phosphorylation and dephsophorylation of specific amino acid residues by Cyclin-Activating Kinase (CAK) and the wee1 protein
2) ENable CDK!-cyclin B formation (aka MPF)
3) Allows G2-M phase transition
What occurs during the metaphase/spindle checkpoint?
1) Chromosomes assemble of metaphase plate
2) Anaphase-promoting complex (APC) activated
3) Degrades cyclin B = MPF diassembly
4) Relieves inhibition of ‘separase’ = spindle cut
5) Sister chromatid separation = anaphase entyry.
How do cytogeneticists manipulate the cell cycle in rder to produce high quality metaphase preparations?
Mitogens - used to induce division of resting cells e.g. PHA
SYnchronisation - inhibitors block cell cycle during S phase by slowing/stopping DNA synthesis (e.g. BrDu)
Block released after 16-22hours cell continue through G” together
Colcemid arrests the cell during mitosis by prevents spindle fibre apparatus fomration.
What are some of the roles of p53?
Controlling progression through G1/S and G2/M checkpoints
DNA damage activates p53 which inhibits progression through the checkpoint.