Cell Division Flashcards
Cyclins regulate the cell cycle via …
… CDKs
Cyclins
- Cyclins accumulate in different stages of the cell cycle.
- Bind and activate cyclin dependent kinases, CDKs.
- Cyclins are targeted for destruction by ubiquitination.
Cyclin-CDK complexes phosphorylate key players in all stages of the cell cycle:
- Initiate DNA replication
- Nuclear envelope breakdown
- Chromosome separation
Cyclin-CDK activities are further regulated by …
… phosphorylation (both positive and negative)
Cyclins targeted for destruction by ubiquitination
- point of no return from one stage to the next
- APC/C targets proteins for degradation
- Adding the small molecule ubiquitin to a protein is the signal for it to be destroyed by the proteosome
Faithful replication and separation of genome
- Replicate all the DNA, one time only: S-phase (synthesis)
- Divide the copies from one nucleus into two: M-phase (mitosis)
Origins of replication
- “fire” once per S-phase
- Cyclin-cdk targeted for destruction by APC/C
If you remove a protein that activates the APC/C and Emi1, replication origins keep firing, this causes the cells re-replicate DNA but never divide.
Homologous chromosomes
- One maternal
- One paternal
Sister chromatids
- Two copies of replicated chromosomes
- Two maternal, two paternal
- Kept together by cohesin rings
M-phase
- Mitosis
- Polarisation of the microtubules into a bipolar spindle.
- Process begins in the S-phase with the duplication of the centrioloes and centrosome.
Centrosome
Centrioles + mass of proteins called pericentriolar material
Centrioles
- Comprised of microtubule array.
- Mother and daughter.
- Duplicated in S-phase
Mitosis
- Ensures the accurate partitioning of the genome to daughter cells.
- Shortest stage of the cell cycle
- Dynamic, highly ordered process
- Six phases
Phases of Mitosis
- Prophase: pro- “before”
- Prometaphase: pro- “before” metaphase
- Metaphase: meta- “adjacent”
- Anaphase: ana- “back”
- Telophase: telos- “end”
- Cytokinesis: cyto- “cell” + -kinesis “movement”
Prophase
- Chromosome condensation begins
- Centrosomes move apart, begin to form mitotic spindle
- At this point, the nuclear envelope is still intact.
Cohesin
Holds sister chromatids together
Condensins
- Similar ring structure to cohesins
- Further loop chromatin into tight bundles
Prometaphase
- Condensed chromosomes attach to microtubules.
- The MTs are growing.
- Nucleus envelope breaks down:
- Phosphorylation of lamins by cyclin B-CDK1
- Leads to disassembly of lamins.
- Nuclear pore complexes (phosphorylated) disassemble.
Metaphase
- Sister chromatids line up on the metaphase plate.
- Dynamic instability cause the MTs to grow slowly, shrink rapidly.
- Physical force from dynamic MTs orients the mitotic spindle.
- MTs reaching for the central chromasomes.
- Sliding of antiparallel MTs at the equator
Metaphase plate
Equator between two poles
Kinetochore
- Protein complex linking chromatin and microtubules.
- Large multimeric complex of structural and signalling proteins.
- Sensor proteins that monitor attachment and sense tension to microtubules.
- Force of microtubule dynamics pushes/pulls chromatids.
- Balance of forces when aligned on equator
Spindle Assembly Checkpoint
- Mitotic Checkpoint Complex (MCC): inhibits APC/C when kinetochores are exposed.
- When all kinetochores attached to spindle, the APC/C released and activated and targets securin for degradation. Here the separase is free to cleave cohesins
- Negative feedback loop: Just one exposed kinetochore stops APC and the signal amplified through kinases.
Anaphase
- Cohesins holding sister chromatids together degraded.
- Sister chromatids move to opposite poles.
- Very fast! (for cells)
Telophase
- Nuclear envelope re-forms and assembles around individual chromosomes.
- Microtubules bundle and push nuclei apart.
- Contractile ring begins to form on midline, and will become the cleavage furrow.
Cytokinesis
- Contractile ring cinches and pinches
- Actin-myosin fibres slide against one another
- Midbody forms at scission point
- Can take a long time to for cells to completely detach
- Failure of this stage leads to binucleate cells
Mitosis produces…
- Diploid cells with identical genetic material to the original cell
- Diploid (2n) = two copies of every chromosome, maternal and paternal
- DNA replicated once and only once in S-phase
- Chromosomes segregated equally
Meiosis produces…
- Haploid cells with genetic material for sexual reproduction
- Haploid (1n) = one copy of each chromosome (haploos, “single”)
- Gamete: sperm or egg (gamos/gamete, “marriage/spouse”)
- Gamete + gamete = zygote (zygon, “yoke, join”)
- Homologous chromosomes segregated
- Mixing of DNA between homologous chromosomes
Oogenesis
- One haploid egg cell per meiosis
- Half of chromosomes disposed of in polar bodies after metaphase I and II
- Oocyte meiosis arrests in metaphase II until fertilisation
- Never completes if unfertilised
Homologous chromosome pairing
- Occurs in the first half of meiosis:
- Pair via complementary DNA sequences
- Two pairs of sister chromatids form a four-chromosome bivalent joined by synaptonemal complex.
- Process called synapsis.
- Homologous chromosomes can then swap genetic material.
Crossing over
- Swapping of genetic material between maternal and paternal chromosomes
- Only about 10% of the time
- At least one per chromosome
- Somehow cells ensure that crossovers do not occur near one another.
Genetic diversification
- Independent assortment of maternal and paternal chromosomes
- Crossing over
- Gene conversion
Gene conversion
- Non-crossing over homologous recombination
- Copy maternal sequence into paternal chromosome, or vice versa
Non-disjunction
- When chromosome segregation goes wrong.
- Down syndrome – trisomy 21 (very small chromosome)
- Trisomy 18 or 13 - usually mosaic (complete trisomies nonviable)
- Turner syndrome – one X, developmental problems
- Klinefelter syndrome – XXY (infertility)
- XYY – no severe symptoms