unit 8 - cell cycle Flashcards
how long does it take to complete the cell cycle?
24 hours
* G1: 12 hours
* S: 7 hours
* G2: 4 hours
* M: 1 hour
how much of the cell’s life is spent in interphase?
90-95%
G1 phase (first gap)
kind of the default stage. after cells are produced by mitosis, they grow until they reach their mature size. acquire nutrients, oxygen, and signals from the environment. continue in G1 phase until a signal (growth factors and hormones, mitogens) is recieved to induce division (unless conditions are unfavorable– low oxygen, too much waste, not enough nutrients, high pH. in this case, they remain in G1 phase or enter G0)
G0 phase (resting phase)
- cells without growth factors can enter G0 and remain there for long periods of time without proliferating– weeks, months, or the lifetime of the organism
- leave G0 when stimulated by the right growth factors
- neurons, muscle cells are usually in G0, other cells switch on and off
S phase (synthesis phase)
- cell enters this phase if it recieves the signal to divide
- DNA replication that results in two identical sister chromatids that are attached at the centromeric region (but they’re not condensed yet. but the DNA is duplicated)
- duplication of the centriole pair in the microtubule-organizing center
G2 phase (second gap)
- cell replenishes energy stores
- synthesizing of proteins needed for chromosome condensation/movement
- some cell organelles are duplicated
- cell contents are reorganized in preparation for mitosis
- ends when mitosis begins
M phase (mitotic phase)
- prophase
* microtubules extend from centrosomes to form the mitotic spindle
* centrosomes are pushed to opposite ends of the cell
* chromatin condenses into chromosomes
*nuclear envelope breaks apart - prometaphase
* spindle fibers attach to the centrosomes of each sister chromatid - metaphase
* chromosomes are aranged in a line at the center of the cell - anaphase
* sister chromatids are separated by shortening microtubules
* the outer edges of the mitotic spindle continue to lengthen and push the two poles away from each other - telophase
* chromosomes start to de-condense
* two new nuclear envelopes form
cytokinesis
separation into two daughter cells. happens via a cleavage furrow in animal cells, which is caused by a contractile ring of actin as it treadmills and pinches the membrane in two
cell division in embryonic cells
- early embryo cells divide much more rapidly, in only 30 minutes
- formation of blastocyst
- skip the G1 and G2 phases and alternate between M and S phases. since they don’t have time to grow in between the cells get smaller and smaller over the rounds of cell division
how is the cell cycle controlled?
through checkpointsthat monitor for:
* optimal extracellular environment for cell growth
* presence of growth factors
* internal conditions, integrity of DNA
controlled by regulatory proteins and molecular brakes that can halt the cycle at each of three checkpoints, guarantees that events of the cell cycle occur in the right sequence and that each process has been completed before the next one begins
G1/S checkpoint
cell monitors size (has it grown big enough?), DNA integrity (is any DNA damaged and in need of repair?), environmental conditions (enough nutrients and oxygen, right pH, not too much waste?), and signalling (presence of growth factors?). if something is wrong, there isn’t a ‘proceed’ signal and the cell goes into G0
G2/M checkpoint
cell monitors DNA synthesis (did all of the DNA copy?) and checks for damage and mutations. if something is wrong, cell attempts to complete DNA replication/repair, and undergoes apoptosis if that doesn’t work, since it’s too late to revert back to G1 or G0 phase.
tumor suppressor proteins are in which groups?
Ink4 or Cip/Kip families
M checkpoint (spindle checkpoint)
occurs near the end of metaphase. determines if all sister chromatids are correctly attached to the spindle microtubules, pauses the cycle until the kinetochores of each pair of sister chromatids are anchored to at least two microtubules on opposite ends of the cell. does this by scanning for straggler chromosomes that are floating instead of attached to microtubules. ensures proper distribution of chromosomes to daughter cells
what is the most important regulator of the cell cycle?
cyclins and cyclin-dependent kinases
* cyclins: proteins that bind to cyclin-dependent kinases
* cyclin-dependent kinases: phosphorylate specific target proteins to turn them on and allow passage to the next stage of the cell cycle
cyclin expression cycle
4 categories of cyclins, whose concentrations fluctuate through the cell cycle
* cyclins activate and direct protein kinases that control passage through the checkpoints
1. G1 cyclin
2. G1/S cyclin
3. S cyclin
4. M cyclin
accumulation of cyclins just before each checkpoint, then a sharp decline as they are degraded
activity of CDKs
- always present in the cell, usually in inactive form. active site containing ATP that transfers P groups to proteins is blocked by the “activation loop”/”T loop”
- become active when bound to cyclins and activated by a CDK-activating kinase. binding pulls the T loop away from the active site to expose ATP. CDK-activating kinase adds a phosphate group to a threonine in the activation loop to stabilize it
- active form adds P group to target enzymes to activate them and progress the cell cycle
- same CDKs, different cyclins to target different proteins in different phases of the cell cycle
molecular brakes: how are cyclin-CDKs turned off?
- degrade cyclins - ubiquitin tags are attached to cyclin to target them to proteosomes, where they are degraded. cyclin levels fall and CDK returns to inactive form
- dephosphorylzation of CDKs
- block cyclins/CDKs with inhibitors–blocks assembly or activity of the complex
- also known as tumor supressor proteins, most commonly in Ink4 or Cip/Kip families
CDK inhibitors p21and p53
production of p21 is controlled by transcription factor p53
* acts on the G1 checkpoint
* if DNA damage is detected, p53 halts cell cycle and recruits enzymes to repair the DNA, or p53 triggers apopsosis if the DNA can’t be repaired
* p53 levels rise when cell is stressed, transcription of p21 is activated
* p21 binds to G1 and S CDK/cyclin complexes and inhibiting them
* p53 is a tumor suppressor gene
* missing or defective/mutated p53 leads to unregulated replication of damaged DNA, which can lead to cancerous cells or mutated proteins. defective p53 is found in half of all cancers.
apoptosis vs. necrosis
necrosis:
* cell explodes/bursts, cell contents spill out
* triggers inflammation
* involuntary
apoptosis:
* voluntary and carefully regulated–programmed cell death
* no cell content spillage, no inflammatory response
factors that cause necrosis
- ischemia (interruption of blood flow) and hypoxia
- nutrient deficiencies, especially glucose
- toxins like venom, carbon monoxide, lead
- infections and immune responses
- physical/mechanical (temperature, electrical, radiation, mechanical stress)
events of apoptosis
- DNA fragments and chromatin condenses
- organelles shrink, nuclear envelope disassembles, nucleus fragments
- cytoskeleton collapses
- cell shrinks and fragments into membrane-enclosed apoptotic pathways
- apoptotic bodies cell display an eat-me signal to phagocytes, cell breaks into smaller apoptotic bodies but cell contents stay intact
intrinsic pathway of apoptosis
what “eat-me” signal is found in apoptotic bodies?
phosphatidylserine – usually restricted to inside of plasma membrane but flips out to the cell surface during apoptosis
* translocated to cell surface by scramblase (activated by caspases)
caspases
protease/degradase enzymes responsible for apoptosis. encoded by gene ced-3
* synthesized as inactive precursors (procapases)
- digest the cell from the inside
- degrade 100+ target proteins
- cleaves nuclear lamina
- activates endonucleases that digest DNA and RNA
- degrades cytoskeleton, causes blebbing of plasma membrane and fragmentation, which triggers the formation of apoptotic bodies
- cleaves organelles
