(bio) unit 7 - Eukaryotic Cell Cycle Flashcards
Unicellular in cell division
generates complete new organism
Metazoans in cell division
many cell divisions required to generate new organism from fertilized egg
Universal features of cell division
- must accurately replicate DNA
- replicated DNA accurately distributed to daughter cells
- most cells duplicate other macromolecules/ organelles + double in size before they divide
mitosis? what is it accompanied by
- division of genetic material that produces daughter cells
- genetically identical to parent cell
- accompanied by cytokinesis (division of cytoplasm into 2 daughter cells)
Where are chromosomes housed?
housed in nucleus
What key events is cell division essential for in eukaryotes (3)?
- Growth and development
- Asexual reproduction
- wear ‘n’ tear, wound repair
Describe the packaging of DNA in eukaryotes
DNA double helix wrapped around histone proteins, which need to be brought into nucleus
What form must DNA be in to become visible in light microscopy
an entire mitotic chromosome that intends on dividing
Homologous chromosomes vs Sister chromatids
one chromosome consists of two sister chromatids
What are the three major stages of the cell cycle?
- Interphase
- M Phase
- Interphase (again)
What subphases exist in Interphase?
G1 , S Phase and G2
What major phases makes up the process of mitosis
M Phase and Interphase
Which major phase does the cell spend the longest time in
G1 phase in the Interphase
What does the cell consist of in the G1 phase of Interphase? What is it called in this stage of the cell cycle?
- Called parent cell
- consists of 2 unreplicated chromosomes
What does the cell consist of in the S Phase and G2 Phase of Interphase? What is it called in this stage of the cell cycle?
- called parent cell
- contains 2 replicated chromosomes with sister chromatids
- 2x DNA content
What does the cell consist of in the M Phase, how does a cell reach that stage?
- highly condensed chromosomes
- mitotic spindle
- A cell reaches M Phase by undergoing mitosis
What process is followed by the mitosis? What stages from the cell cycle are involved
Cell division from the M Phase, back to interphase
What happens during the S Phase of the cell cycle
chromosome replication (DNA copied) during S-phase to create the sister chromatids
What happens during the G1 phase of the cell cycle
Where most of the cell growth occur
What happens during the G2 phase of the cell cycle
Cell completes preparations for mitosis:
- chromosomes condense
- spindle apparatus start to condense
What happens during the M phase of the cell cycle
mitosis (division of nucleus) and cytokinesis (division of cytoplasm)
What are the two transient cytoskeletal strucutres that are required for cell division in eukaryotes?
- Microtubules of the mitotic spindle
- Actin and myosin filaments of the contractile ring
Why is there a lot of ‘tubulin’ protein synthesized during G2
for the building of the spindle microtubules to interact with chromosomes during mitosis (M phase)
Function of actin and myosin filaments of the contractile ring
they are cytoskeletal elements involved in the formation of the contractile ring to split the cell during M phase.
Describe cytokinesis in Animal cells
A cleavage furrow is created by a ring of actin filaments just under the plasma membrane
Describe cytokinesis in plant cells
At the end of mitosis (anaphase) a new cell wall must be constructed between dividing plant cells
- this is done by the vesicles from the Golgi that lays down matrix for new cell wall, occurs during Telophase
What happens during prophase stage of mitosis
- early mitotic spindle develops
- replicated DNA are now chromosomes w sister chromatids and centromeres in the middle
What happens during the prometaphase stage of mitosis
A component of the mitotic spindle, kinetichore microtubule attaches to the centromeres of the chromosome to organize them by pulling them apart.
The nuclear envelope has broken down
Importance of kinetochore in a metaphase chromosome
Responsible for the proper allocation of chromosomes to daughter cells
Three major stages of mitosis after pro metaphase, and describe them
- Metaphase - chromosomes migrate to the equator of the cell
- Anaphase - sister chromatids separate
- Telophase and cytokinesis - nuclear envelope reforms , spindles disintegrates
Meiosis
- division of genetic material to produce daughter cells with half the genetic material from parent cell
- production of gametes (eggs and sperm)
- basis of sexual reproduction and genetic inheritance
difference between meiosis and mitosis
Mitosis:
- separation of chromatids
- results in the formation of identical daughter cells that line up on metaphase plates
Meiosis:
- separation of homologues
- random allocation
- parent homologues associate with eachother along metaphase
What is the stage in meiosis/sexual reproduction that creates the synapses and crossing over?
Prophase I
- the coming together of parental homologues to create connections/cross overs aka “chiasma”
What is the protein complex that holds parental homologues together during prophase I of meiosis I
synaptonemal complex
Distinguish early prophase I to late prophase I during meiosis
Early prophase I:
- chromosomes condense
- nuclear envelope breaks up
- spindle forms
- SYNAPSIS OF HOMOLOGS
Late prophase I:
- crossing over of non-sister chromatids
- recombination of genes
Describe Metaphase I in Meiosis 1
- chromosomes line up along the metaphase plate to recombine
Describe Anaphase I in Meiosis 1
- separate parental homologues
Describe Telophase and Cytokinesis in Meiosis 1
- chromosomes move to the opposite side of cell
- DNA is doubled but ar very different
Difference in separation of homologs in Meiosis I vs Meiosis II
Meiosis I: separation of homologs
Meiosis II: separation of chromatids (similar to mitotic division)
Mistakes in meiosis? What does this lead to
- improper allocation of chromosomes to each daughter cell
- gametes with an unusual number of a particular chromosome - “aneuploidy”
Non-disjunction of chromosome 21 in Meiosis I, what does the process involve
- During S-phase there is a meiotic division I and non disjuction.
- Results in an aneuploid gametes with 2 copies chromosome 21
- Also results in gametes without any copy of chromosome 21
How does Meiosis and sexual reproduction create offspring with genetic variability? (3)
- recombination during prophase I
- Independent assortment of (recombined) homologs during meta/ana/telophase of meiosis I
- Independent assortment of (recombined) chromatids during meta/ana/telophase of meiosis II
Alternatives to meiosis: Asexual reproduction
- an organism well adapted to their environement can clone itself at a fast rate
Advantage of sexual reproduction
- genetic variability if the environment changes
Is the cell cycle the same in all cell? What are some factors to consider? Give examples
No, the do not all follow the pattern of continuous division..
- depends on cell type, developmental age, and external signals
- neurons never divide once fully matured, they are “terminally differentiated”, and will die if they do not work
- human embryo continues to divide until they reach a normal somatic size
What is an example of cells continuously dividing at a high rate
epithelial lingins of intestine
Purpose of G0 phase in cell cycle
“stall” in G1 phase , cells opt out of cell cycle and do not divide
- instead perform regulatory/cel functions
- but can be induced to re-enter cell cycle
Maturation Promoting Factor (MPF)
A factor that pushes the cell to undergo mitosis
What are the two components of the Maturation Promoting Factor? What process are these two components followed by?
- Cyclin-dependent kinase (Cdk) - catalytic subunit that transfers PO4 to certain areas on target protein
- Cyclin - regulatory subunit that drives Cdk activity by having osciallation levels
Followed by the activation of downstream targets to push cell to mitosis
t/f different class of cyclin-Cdk complexes trigger different steps in the cell cycle
t : different kinases are dependent on different cyclin-regulatory subunits
3 ways to regulate Cdk activity to control cell cycle progression
- Change levels of cyclin partner
- can increase/decrease activity with cyclin expression - Addition/removal of inhibitory phosphate groups
- can increase/decrease activity with the regulation of phosphate - Presence/absence of inhibitory protein
- can increase/decrease activity with regulation of Cdk inhibitors bound to cyclin-Cdk
Describe how the cell can regulate Cdk activity by destruction of cyclin, when does this process occur?
Destruction of the cyclin inactivates Cdk
- this is done by the tagging of the ubiquitin chain to the cyclin , which is a process pushed by the anaphase promoting complex (APC)
- Cdk becomes inactive
Process occurs to allow cell to complete the M-phase and enter anaphase if theres a drop in M-Cdk activity
Explain how the cell is driven from anaphase, to completion of M phase to G1 phase (the destruction of cyclin/inactivation of Cdk)
- there is an increased transcription of M-cyclin gene through the M phase
- leads to the gradual rise in M-Cdk activity
- a targeted destruction of M-cyclin protein by Anaphase Promoting Complex (APC)
- this process involves tagging a ‘ubiquitin’ to the M-cyclin
- results in a sudden drop in M-Cdk activity which allows cells to enter anaphase / completes M phase
How can cells regulate Cdk activity by the addition/removal of inhibitory phosphate groups
- increased by the removal of an inhibitory phosphate
- decrease by the addition of a phosphate which inhibits the M-Cdk from becoming active
How can cells regulate Cdk activity by the presence/absence of inhibitory protein
an active cyclin-Cdk complex is inactive once inhibitor protein is attached
- this can block entry into the S phase , keeping cells in G1
What are the 3 transition points that allow cell cycle to be paused and what are the three mechanisms involved to pause it?
- “G1/S Checkpoint” Progress from G1 phase to S phase: determined by the activity of Cdk inhibitor proteins.
when active: blocks the transition
- “G2/M checkpoint” Progress from G2 phase to M phase: determined by the inhibition of activating phosphatase.
when active: PO4 would come off by the phosphatase and allow transition
- “Spindle Checkpoint” Progress from the M phase to prophase and G phase: determined by the inhibition of APC activation.
when active: the addition of a ubiquitin tag would stop the M-Cdk activity via APC and allow transition into prophase
Why are there molecular brakes in the cell cycle?
To determine if cells can continue the cell cycle at key points
What needs to be considered at the G1/S Checkpoint?
- If the environment is favourable/resources available for division
- is there an external signal telling the cell to divide
slide 58
What needs to be considered at the G2/M Checkpoint?
- If all DNA is replicated
- if all DNA damage is repaired?
- is activated MPF present?
What needs to be considered at the Spindle Checkpoint?
- Are all chromosomes properly attached to the mitotic spindle
- have all chromosomes moved to the metaphase plate
- Are they all aligned
Features in cell cycle that is associated with cancer
- failure to respect checkpoints
- cell division is occuring in the absence of signals
- inappropriate ‘start’ signals
- failure to induce death to damaged cells despite DNA failure
What is the p53 gene? What if it is defective
a tumor suppressor gene that detects DNA damage at the G1/S checkpoint
- leads to the synthesis of inhibitor of G1/S and S-Cdk
- defective p53 is associated with cancer
When DNA damage is detected, when should the cell cycle stop
G1 , see slide 64
What is an accelerator in the cell cycle
Mitogens (signal that binds to cell surface receptor) that activate gene transcription factors that drive expression of genes that promote progression of G1 to S-Phase
see slide 67 for diagram
What is a Brake in the cell cycle ? Give an example
- Protein that binds and inactivates accelerator transcription facts during G1.
- blocks transcription of S-phase genes
ex. Rb (retinoblastoma) protein
see slide 67 for diagram
Describe the reasons behind the dysregulation of cell cycle “accelerators”
- over expression of signals promoting cell cycle
- mutations in signal molecules, receptors, that are in the downstream pathway
cell division is no longer controlled once it starts - ignores quality control
What is a oncogene (oncoprotein), what is its non mutated version called?
Mutated versions of normal genes/ proteins invovled in regulating cell division/proliferation, has the potential to cause cancer
non mutated version - proto-oncogene
How does cancer start? (3)
- failure to respect cell cycle checkpoints
- cells become genetically unstable once uncontrolled division starts , which accumulates more mutations
- combination of errors
What is apoptosis
- programmed cell death
- getting rid of unwanted cells
- organized process
Necrosis
- messy cell death
What family of proteins regulates Apoptosis? Pro-death and anit-death?
Bcl-2 family of proteins
Pro-apoptotic:
- Bax, Bak, Bad
Anti-apoptotic
- Bcl-2
What causes cell death (4) ?
- cell stress
- DNA damage
- free radicals
- lack of ‘survival factors’
What is Caspase?
- Family of enzymes that are activated in response to apoptic signals
What is caspase cascade ? What occurs in it?
A series of activation of three levels of caspase enzyme (x, y, z)
- activation of caspase Y: cleavage of nuclear lamin
- activation of caspase z: cleavage of cytosolic protein
What is released to trigger Apoptosis? Where does this occur?
- Cytochrome C is in the intermembrane space of the mitochondria and is activated once it leaves the cell
- adaptor protein in the cytosol will be activated when cytochrome c binds to it
- this assembles a large protein structure apoptosome
- begins caspase cascade that leads to apoptosis
What are needed to increase cell number and/or size? (3)
- Survival factors to prevent apoptosis
- Mitogens drives the cell cycle - proliferation
- growth factors to increase size
What is the general term for a gene that normally drives cell division; a gain-of-function mutation in this type of
gene can drive a cell toward cancer
proto-oncogene
a family of proteases that plays a key role in programmed cell death
proteolytic enzymes called caspases
