Cell replication (6) Flashcards
What is the cell cycle?
orderly sequence of events in which a cell duplicates its contents and divides in two
What are the phases of the cell cycle?
- M-phase (mitosis): nuclear division and cytokinesis
- Interphase: duplication of DNA, organelles and protein synthesis
What are the stages of interphase?
G0: cell machinery dismantled
G1: decision point, cell gets larger, copies organelles
S phase: synthesis of DNA/proteins
G2: decision point, cell grows more, makes proteins and organelles, prepares for mitosis
What is a centrosome?
- pair of centrioles: daughter and mother–> each consists of a barrel of 9 triplet microtubules
- organises mitotic spindle
What are the phases of mitosis?
- prophase: nuclear membrane disintegrates, chromosomes condense, each w/ 2 sister chromatids, held together by a kinetochore, and duplicated centrosomes migrate to opposite poles
- metaphase: chromosomes migrate to equator, each centrosome attaches spindle fibres to centromeres
- anaphase: breakdown of cohesin, centrosomes pull sister chromatids apart
- telophase: nuclear membranes reform
- cytokinesis: cell membrane pinches in and daughter cells separate at acto-myosin contractile ring, leaving midbody, which eventually disintegrates
What are radial microtubule arrays (ASTERS)?
microtubule organising centres that form around each centrosome–> grow until radial arrays meet at centre–> polar microtubules form
What is the Spindle Assembly checkpoint?
- between metaphase and anaphase
- check that every chromatid is bound to a microtubule coming from its own hole
- BUB protein kinases dissociate from kinetochore when chromatids are properly attached to spindle–> stops sending signals
- also CENP-E signal
In what ways can mis-attachment of microtubules to kinetochores lead to aneuploidy?
- amphelic= normal attachment–> kinetochores do not produce a checkpoint signal
- monotelic attachment= only 1 kinetochore in the pair is attached
- syntelic attachment= both kinetochores attached to MTs from same centrosome
- merotelic attachment= a sister chromatid is attached to both centrosomes, so gets pulled and breaks
What happens if there is aberrant centrosome replication?
- too many centrosomes–> multipolar spindle–> aberrant cytokinesis
What happens if a cell is not big enough or has DNA damage?
- detected at checkpoints: G1 and spindle check point
- cell cycle progression is halted and cell enters G0 to repair DNA or undergoes programmed cell death/ apoptosis if DNA damage too great or there are chromosomal abnormalities
What are the checkpoints of the cell cycle?
- G2 checkpoint: for DNA damage before entering mitosis
- metaphase-anaphase checkpoint: for sister chromatid alignment
- G1 checkpoint: for growth factors
- tumours can block checkpoints
What are protein kinase cascades?
- signal amplification
- kinases switched on, regulating other kinases etc…
- phosphorylation reversed by phosphatases
What is c-Myc?
- oncogene- overexpressed in many tumours
- a transcription factor- stimulates the expression of cell cycle genes
- inc. [cMyc] in presence of growth factors
What are cyclin-dependent kinases?
- Cdk1, Cdk2, Cdk4, Cdk6
- present throughout cell cycle
- Cdks phosphorylate cell, signalling that it is ready to pass into the next stage of the cell cycle
- dependent on cyclins, which bind to Cdks, activating them to phosphorylate other molecules
What are cyclins?
- cyclinA, cyclinB, cyclinD, cyclinE
- only present at specific points in cell cycle
- undergo a constant cycle of synthesis and degradation during cell division
