Mitosis Flashcards
Cell phases
G1 - growth, longest phase by far
S - synthesis, replication of chromosomes and centrioles
G2 - growth, duplication of organelles, proteins for mitosis
M - mitosis, very short
Functions of mitosis
Replicate DNA accurately, segregate chromosomes, replicate cell structures, divide cells
Karyokinesis
Division of nucleus
Cytokinesis
Division of cytoplasm and cell contents
Interphase
Includes G1, S, G2
G0 if cell has left cycle
Duplication of centrioles
Pair splits, each becomes nidus for new centriole
Reform gamma tubulin and capping proteins
MTs nucleate through gamma tubulin rings
Deviations from cell cycle
G0 - quiescent phase (not good environment)
Gtd - terminal differentiation (muscles, nerves)
Prophase
Chromatin condenses to chromosomes, nucleolus breaks down
Centrioles migrate, MTs develop
Late prophase - nuclear envelope breaks down
Chromosome condensation
Condensin increases coiling
Cohesin binds sister chromosomes
Dissolution of nuclear envelope
Occurs during “prometaphase”
M-CDK phosphorylates lamin
Breaks into small vesicles of lamin + membrane
Allows fast reassembly after mitosis complete
Microtubules during mitosis
Astral
Polar (connect MT to MT in spindle, push against each other to separate centrosomes)
Kinetochore (pull chromosomes towards centrosome)
Metaphase
Chromosomes migrate and align at equator of spindle via MT “tug of war”
MT’s attach to kinetochores
Centromere
Region where sister chromosomes attach (DNA)
Kinetochore is complex of 30+ proteins that attach centromere to microtubules (plate structure)
Separation of chromatids
Anaphase promoting complex (APC) is phosphorylated when aligned
Ubiquitinates securin which is inhibitor of a cohesin protease
Securin destroyed ->protease active -> cleaves cohesin
Anaphase
A - chromosomes to centrosome via depolymerization of kinetochore MTs and dyneins on astral
B - poles apart via kinesins on polar MTs
Telophase
MT’s depolymerize
Lamin, pore complexes dephosphorylated - nuclear membrane reforms
Chromosomes decondense
Actin contractile ring -> cytokinesis
Time of mitosis
Very short! 2-3 hours total
G1 determines whether rate of cell division
Cells that get to G2 will go through mitosis
Telomeres
Repeating sequences
Not always transcribed -> aging
Telomerase rebuilds and can extend lifespan
Regulation of cell cycle
Cyclins only present for short time, activate CDKs CDKs always present, but must bind to cyclin to be active Also regulated by phosphorylation (checkpoints) Many targets (transcription factors, kinases, activate other cyclins)
Conserved across species
Can cause cancer…
S cyclin
Initiates DNA replication (S phase)
Joins with s-CDK
Phosphorylates pre-replicative complex which normally inhibits
Allows origin of replication complex (ORC) to begin fx
Cyclins
Only present for short period - translated, then ubiquitinated
Carry out function via CDK
Checkpoints
Regulate cyclins and CDKs based on "quality control" G1 - env't favorable? S - DNA damage? G2 - DNA replicated? M - sister chromosomes at equator?
Retinoblastoma
Inhibits transcription of proliferative proteins (via inhibition of transcription regulators) based on env’t
G1/S cdk inactivates by phosphorylation, allowing replication to begin
Defects cause proliferation despite env’t (cancer)
p53 mechanism
Always translated and broken down in cell
p53 is phosphorylated and stabilized if cell stress or DNA damage
Transcription upregulator of p21, which binds and inhibits G1/S-cdk
Also can initiate apoptosis
Most common cancer mutation (most cells)
