Lecture 7: Cell Cycles Flashcards
How did you get to where you are
1) growth
2) divison
DNA in prokaryotes
- DNA as hereditary information
- Vast majority have singular circular DNA (bacterial chromosome)
the rate at which prokaryotic cells divide
maximum rate where DNA replication occupies most of period between cytoplasmic divisions
when replication is complete
cytoplasm divides
the bacterial cell cycle (3 periods)
1) growth of cells and initiation of DNA replication at origin of replication site (ORI)
2) DNA replication
3) Cell divides by binary fission
What is the origin of replication site
ORI (nucleotide site where replication originally starts)
- in the middle of the cell where enzymes for DNA replication are located
- Ori is at the middle because the enzymes are at the middle
Binary fission
division of cytoplasm to divide cells and chromosomes, where each cell gets 1 chromosome (for prokaryotes)
Step 1 of bacterial replication
INITIATION OF REPLICATION
- replication of bacterial chromosome begins at ORI
Step 2 of bacterial replication
DNA REPLICATION
- once the original duplicates, 2 ori’s will migrate towards the two ends of the cell as the rest of the chromosome is replicated
- active movement distributes two replicated chromosomes to two ends of cell (on opposite ends)
Cell Cycle
a period of growth followed by nuclear division and cytokinesis
- eukaryotes: mitosis and meiosis
Eukaryotic Cell Cycle
- multicellular eukaryotic organisms require strict control of cell division (out of ctrl growth can lead to tumors/cancer)
- ultimately results in a mature body composed of different subpopulations of cells (i.e. WBC, rbc, skin cells that are formed through mitosis are the same genetically but are specialized, so they have different functions)
Step 3 of Bacterial replication
CYTOPLASMIC DIVISION
- inward growth of plasma membrane leads to pinching to eventually produce 2 daughter cells
- new cell wall material assembled
- cut cell into 2 parts (binary fission)
Cell Division
Mitosis: divides replicated DNA equally and precisely
- genetically similar to original cell (CLONE)
Meiosis: daughter cells with 1/2 the number of chromosomes
- genetically different from original cell
Clone
- genetically similar to original cell
essentially produces through mitosis, but the specialization makes the cells different but they are genetic clones
Difference between mitosis and meiosis
1) MITOSIS
- 2 new daughter cells
- clones
2) MEIOSIS
- 4 daughter cells
- 1/2 the number of chromosomes from parents: good because it makes them different genetically allowing for variation
DNA of eukaryotic cells
- divided among individual, linear chromosomes
- located in cell nucleus
what are chromosomes
nuclear units of genetic information that are divided and distributed
what is Ploidy
number of chromosome sets (cell or species)
- diploid (2n)
- haploid (n)
Diploid
humans: in majority of cells we will have 2 sets of chromosomes (46 chromosomes)
Haploid
specific algae, specific protists, prokaryotes will have haploids
Sister chromatids
- Replication of DNA of each individual chromosome forms sister chromatids (2 identical molecules)
- Attached pair of duplicated chromosomes, at this point they’re only considered 1 chromosomes (they’re formed before forming new cells, its just the product of multiplying chromosomes)
Polyploidy
multiple chromosome sets
- triploid and tetraploid are also possible, plant species
Non homologous
Chromosome with different genes
- chromosome 4 and 19 for example are non-homologs
Homologs chromosomes
chromosomes have same genes arranged in same order
Ex. the pair within a set
For ex: We have diploids: such as 2 chromosome 11’s those are homologs, they are the same gene arranged in the same order
sister chromatids are 2 ____ molecules
2 identical molecules
Sister chromatids eventually become
independent daughter cells
Mitotic cell cycle
-2 major phases: interphase (period of growth) and mitosis (period of division)
MITOSIS HAS 5 PHASES
1) prophase
2) prometaphase
3) metaphase
4) anaphase
5) telophase
Chromosome segregation
Separation of sister chromatids and equal distribution to each of 2 cells resulting from cell division
G1
*period of growth before DNA replicates
- majority of growth occurs here
- spend most of their time here: amount of time depends on the
the time spent in G1 depends on
- signals the cell gets
- environment of the cell
- type of cell
G0
- cell cycle arrest
- cell exit cycle:
- no longer participate in cell cycle
what’s an example of a cell that would exit G0
nerve cells
- therefore, its difficult to replace nerve tissue because its hard to replace them since they exit therefore neurodegenerative diseases are hard to treat
Interphase
G1,G2,S (majority of cycle)
G2
- period after DNA replicates
cell prepares for division
SHORT
Mitosis
- cytoplasm divides independent of mitosis beginning but occurs at end of mitosis
where does interphase end
parent cell
Timing for cell cycle
G1: Variable Time
S: 10-12 H
G2: 4-6 H
Mitosis: 1-4 H
Phase 1: Interphase
- G1 PHASE
New cells goes straight here
- Daughter cell from previous
division cycle enters initial period of cytoplasmic growth (building new macromolecules, organelles, etc)
- No DNA replication
GOES TO S commitment
Phase 1: Interphase
- S PHASE
- DNA replication (building new DNA, each chromosome replicates)
- Chromosomes duplicate (stay together at sister chromatids)
Phase 1: Interphase
- G2 PHASE
- synthesize RNA and protein
- NO DNA replication
- Get ready for cell division
building more RNA and DNA to prep for cell
chromosomes in interphase
- during all steps of interphase, chromosomes are relatively loose but organized in nucleus
(loose arrangement)
- DNA wraps itself loosely, because that way enzymes get to DNA in transcription and translation
what happens in S phase (hint: cytoskeleton)
W/ Duplication of chromosomes, centrosomes will also duplicate
- major component of cytoskeleton
- main microtubule organizing center
Mitosis Stage 1: Prophase
- Chromosomes condense into compact rod-like structures
*prevents enzymes from coming on from transcription and replication - Sister chromatids held together by a centromere
region that is in the middle of sister chromatids, holds them together - Spindle forms in the cytoplasm between 2 centrosomes
To build microtubules that make up spindle which moves chromosomes around
why do we want to prevent enzymes for transcription and replication
we are in mitosis, we don’t want this to happen yet, by compacting our chromosomes we can accurately divide so each cell gets the right number of chromosomes
What happens to nuclear envelope around chromosomes
break down
DNA wrapping
- DNA complexed with histone proteins to fit into nucleus
- 2 each of H2A, H2B, H3. H4 histones= 8 protein nucleosome core particle attach to DNA molecule, combined tight loop=nucleosome
- mutliple nucleosomes are coiled and stacked forming chromatin
Histone H1 causes what
nucleosomes to package into a coiled structure (solenoid)
- btw H1 is the 5th type of histone
charge of Nucleosomes and Chromatin Fiber
DNA = sugar and phosphate backbone that have a -q
therefore, the +q of histones attracted to -q of DNA
how exactly do we compact chromosomes
wrapping our DNA makes it compact which sets our chromosomes to be compact
Mitosis Stage 2: Prometaphase
- Nuclear Envelope breaks down and disappears which allows for:
- Spindle entering former nuclear area because
- Microtubules from opposite spindle poles attach to 2 kinetochores of each chromosome (does not attach to DNA)
*kinetochores are on the outside of centromere/chromosome
Kientochores
protein complex that attaches chromosomes to spindle fibers during cell division.
Kinetochore attach the sister chromatids at centromere (complex of different proteins)
Mitosis Stage 3: Metaphase
- Spindle is fully formed
- Chromosomes align at spindle midpoint, moved by spindle microtubules
this is where we do genetic analysis chromosomes are most intense
Karyotype
Importance of karyotypes:
1) determines number of chromosomes in cell
2) size of chromosomes: dependent on number of genes and DNA on chrosomes
- Allows us to determine problems
3) Determines sex of human
When is karyotype checked
Metaphase: bc chromosomes are most condensed and visible, making it easier to observe their structure and number
Mitosis Stage 4: Anaphase
- spindle spectates sister chromatids and moves them to opposite spindle poles
- Chromosome segregation is complete
***(kinetochores are directly involved: help align and separate chromosomes during cell division, ensuring accurate chromosome distribution to daughter cells.)
Mitosis Stage 5: Telophase
Chromosome decondense
- Return to extended state typical of interphase (loose phase)
Spindle Disassembles
- New nuclear envelope forms around chromosomes
- We start division of cytoplasm now
- End of nuclear division yielding 2 nuclei
Cytokinesis
Division of cytoplasm completes cell division
Produces 2 daughter cells:
- each daughter nucleus produces by mitosis
- genetically identical to parental cell
Cytokinesis in Animal Cells
Furrowing : microfilaments are tightened until plasma membrane can be pinched off
Band of microfilaments forms just inside the plasma membrane, forming belt
microfilaments slide together and tighten (become so tight)
- form furrow in plasma membrane
- separates cytoplasm in 2 parts
Cytokinesis in Plants
- vesicles will come from Golgi with cellulose that will fuse to make a new cell wall and divide cell into 2 *
- Cell wall material in deposited along plane of former spindle midpoint
- Deposition continues until continuous new wall (cell plate) separates daughter cells
- stretches across former spindle midpoint
Spindle Formation
1) In Animal Cells
CENTROSOME:
- main microtubule organizing centre (MTOC)
- contain a pair of centrioles
- divides and move apart
Microtubules form early spindle
2) In Plant Cells
NO CENTROSOME:
- spindle forms from multiple MTOCs (still make microtubules and have organizing centres)
- Assemble in all directions surrounding nucleus
what happens in the spindle
kinetochore microtubules will connect chromosomes to spindle pores (binds to sister chromatid)
Nonkinetochore microtubule
- Extend between spindle pores without connecting to chromosomes
- At spindle midpoint, microtubules from 1 pole overlap with those from opposite
As the length of the nonkinetochore microtubules increase
It will stretch the cell which increases the distance between sister chromatids for cytokinesis to happen away from the equator
* don’t touch sister chromatids
How do chromosomes move
Chromosomes move through the shortening of microtubules, aided by motor proteins and enzymes like kinesin and dynein, which help pull them toward opposite poles.
microtubules remain stationary
tubulin- protein that forms microtubules
How do we know microtubules remain stationary
We know microtubules remain stationary because fluorescence-marking experiments reveal that they stay in place while motor proteins move along their length.
- no movement of a bleached site
Cell Cycle CTRL
- complexes of cyclin and a cyclin decedent protein kinase (CDK)
Cyclin: A protein that regulates the cell cycle by activating cyclin-dependent protein kinases.
Cyclin-dependent protein kinase (CDK): An enzyme that, when activated by a cyclin, phosphorylates target proteins to drive cell cycle progression.
CDKs
Activated when combined with a cyclin
- adds PO4 groups to target proteins
Different cyclin and CDK combinations
regulate cell cycle transitions at different checkpoints
- cyclin level fluctuates during cell cycle
- CDK activity levels also fluctuate during cell cycle
IMPACT OF FLUCTUATION:
regulate the cell cycle progression by activating specific target proteins through phosphorylation, with cyclin levels rising and falling at precise stages to ensure proper timing and transition between phases.
FULL CYCLIN/CDK CTRL
(internal mechanisms)
1) DURING G1
- cyclin E levels RISE
- CDK2 activity RISES
= cell passes G1-S checkpoint
2) S CYCLIN BINDS TO CDK2
- cyclin A RISE
- CDK2 activity RISES
= cell completes S Phase
3) ACTIVTED CDK1
- cyclin B levels RISE
- CDK1 activity RISES
= cell passes the G2-M checkpoint
- cyclin is degraded
If a cell passes from G1 to S
it must finish cycle
enzymes that phosphorylate proteins
- only if they’re bound on a cyclin, put through as a combo
we must regulate the cycle because
it will prevent abnormal cell growth
How do we see Contact Inhibition
PETRI DISH
- cells will grow and divide until dish is filled and then contact inhibition
CANCER CELLS
- lost ability of contact inhibition to grow on top of each other which forms tumours
external mechanisms
Based on surface receptors that recognize and bind signals: (can tell cells to speed up, slow down, turn on/off)
- peptide hormones and growth factors
- cell-surface molecules
- molecules of the ECM
- Binding triggers internal reactions that speed, slow, or stop cell divison
- Contact Inhibition- contact triggers a stop cell division response
Contact Inhibition
contact triggers a stop cell division response
- receptors of one cell touch another when too close a cell is signal and the rate of cycle will slow down
Asymmetrical Cell Division
- Stem cells in animals and plants exhibit asymmetrical cell division
- asymmetrical: differ from how many regulatory proteins they have which controls transcription, translation, and gene expression *
- Creates two different pools of daughter cells
1) Progenitor Cell (divides definitely, undergoes specialization)
2) Stem Cell (divides infinite times)
proteins will make a cell become a progenitor cell
in time will become specialized on the path
asymmetrical divison
the proteins they get determines what they are/become
Cells cant divide indefinitely
triggers cellular senescence (cell aging)
- loss of proliferative ability over time
1) DNA damage
- Mutations: issue with duplicating DNA, A threshold of mutations will tell cells to stop growing and dividing so that they mutation doesn’t pass on
2) Telomere shortening
- extensions on end of chromosomes made of nucleotides
Have 0 genes but they protect our genes on our chromosomes so as cells keep dividing, the telomeres keep shortening
- we cant risks the loss of protection, triggering cells to stop and triggers cell aging
Cancer
CTRL of cell division is lost (to respond to internal/external factors to stop cell growth and division)
- cell divide continuously and uncontrollably
- form rapidly growing mass of cells that interfere with body functions
- ONCOGENES: mutated genes that cause cancer
- normally, these are normal genes but they become mutated to cause cancer
Cancer cells break loose from their original tumours in a process called metastasis
- form additional tumours in other parts of the body
Tumours take residence somewhere else in the body
Secondary Tumours
- tumours have a greater density of cells
Apoptosis
programmed cell death
- very ancient mechanism that’s common to all multicellular eukaryotes studied
- initiation of cell death results from internal+external signals
- involves activation of caspases-protease enzyme
Caspases
- triggered by signal transduction and occur in all eukaryotes *
- enzymes that belong to proteases and break down protein in cells
- protein carry out cellular function therefore, enzymes would stop function
BC
- there are times when cells you needed at development are no longer useful
- damaged cells
- cells behaves improperly (precancerous cells)
TRIGGER APOPTOSIS
Nematode Caenorhabditis elegans
Early experiments to model apoptosis
- because its translucent so body could be seen
An Adept Signal
- on surface of mitochondria, adept signals with activation of specific genes
* NUCLEASES will be activates and break down DNA and distrust mitochondria to prevent ATP synthesis)
what do microtubules make up
spindle, move chromosomes around
when nutrients are abundant in prokaryotic cells, what can be observed
not as much of a need for a B period (G1) since they can grow quickly enough to divide their cytoplasm as soon as DNA replication is complete + chromosomes are separate
when the nucleus divides
the chromosomes are segregated
THE 3 STAGES OF MITOSIS AND THE EUK CELL CYCLE
1) elaborate master program of molecular checks and balances to ensure proper progression
2) process of DNA synthesis replicates each chromosomes into 2 perfect copies
3) Structural and mechanical web of interwoven cables and motors of cytoskeleton to separate the replicated DNA into daughter cells
how are newly formed sister chromatids held
via cohesins
- cohesins are removed during mitosis and sister chromatids are thus seperated
- the removal is precise leading to proper distribution of chromosomes=chromosomal segregation
clones are exactly identical t/f
F- genetically very similar but not strictly identical
cells can remain in interphase forever t/f
T
what is a linker
short segment of DNA that extends between nucleosomes
RNA synthesis in mitosis
as DNA is condensed, the nucleolus becomes smaller and eventually disappears, reflecting a shutdown of RNA synthesis
- when chromosomes are decondensation the nucleolus, reappears and RNA transcription resumes (at this point, the cytoskeleton returns to interphase and nuclear division is complete with 2 nuclei)
when Is chromosomal segregation complete
when daughter chromosomes have reached the 2 poles
mitotic spindle
- in cytoplasm, mitotic spindle begins to form between two centrosomes as they migrate towards opposite ends to form spindle poles
mathematical relationship between chromosomes and amount of DNA
- before: 1 chromosome is 1 DNA double helix
- after: 1 chromosomes is 2 DNA double helixes
- DNA replication increases the amount of DNA in the nucleus but NOT THE NUMBER OF CHROMOSOMES
thus, each of the 2 daughter cells receives 1 of the 2 sister chromatids from each replicated chromosome
asters
centrosomes at the spindle tips which form the poles of the spindle
type of centrosome that makes spindle pores
how are microtubules formed in plants
microtubules that assemble in all directions from multiple MTOCs to surround the entire nucleus
what happens to tubulin as the kinetochores pass along the microtubules
the tubulin will disassemble
- microtubules will become shorter
Cell Cycle Arrest Scenarios
G1/S CHECKPOINT
- DNA is damaged by radiation or chemicals
- G1/S is where we read extracellular signals so if we don’t have a necessary signal/hormone=arrest
G2/M CHECKPOINT
- DNA not fully replicated in S
- DNA damage
- we need complete DNA replication
MITOTIC CHECKPOINT
- whether chromosomes are attached properly to mitotic spindle so that they’ll align correctly
- essential for proper number of daughter cells
local area where stem cells divide
niche
