Cell Cycle Control, Cell Growth Regulation, and Cell Death Flashcards
what is the most basic function of the cell cycle
to accurately replicate DNA
what is the duration of the cell cycle
it varies depending on cell type
what are the phases in the eukaryotic cell cycle
- M phase mitosis and cytokinesis
- S phase DNA replication
- G1 and G2 phases cell growth
where are the main cell cycle checkpoints
- late G1 phase
- G2 to M phase
- Mid M phase
what is checked at the late G1 phase checkpoint
ensures favourable environment before DNA replication
what is checked at the G2 to M phase checkpoint
confirms DNA is undamaged and fully replicated
what is checked at the mid M phase checkpoint
chromosomes are appropriately attached to the mitotic spindle before separation
what is the core of the cell cycle control system
- a series of molecular switches that operate in a defined sequence
how is cell cycle machinery regulated
- phosphorylation kinases (type of enzyme that adds phosphates to other molecules)
- dephosphorylation phosphatases
how are the kinases regulated in cell cycle control
by another set of proteins called cyclins
the kinases involved in cell cycle control are referred to as what
cyclin-dependent kinases (Cdks)
the ______ of Cdks is cyclical and the ______ of cyclins is cyclical
- activity
- concentration
what does G1-Cdk do
drive progress through G1 toward S phase
what does G1/S-Cdk do
initiate transition into S phase
what does S-Cdk do
- launch S phase
- trigger DNA replication
what does M-Cdk do
- triggers entry into M phase
- mediate many changes during itosis
what is a cyclin
set of proteins that regulate Cdks
which cyclin is used for G1-Cdk
cyclin D
which cyclin is used for G1/S-Cdk
cyclin E
which cyclin is used for S-Cdk
cyclin A
which cyclin is used for M-Cdk
cyclin B
the [ ] of cyclin ____ due to continual transcription and protein synthesis
increases
the [ ] of cyclin increased due to what
continual transcription and protein synthesis
the [ ] of cyclin ____ due to targeted degradation via ubiquitylation
decreases
the [ ] of cyclin decreases due to what
targeted degradation via ubiquitylation
the activity of Cdks can be modulated by what
- inhibitor proteins
- these block the assembly or activity of cyclin-Cdk complexes
cyclin-Cdk complexes contain what key thing that needs to be removed to make them active
- inhibitory phosphates
- they are removed by phosphatases
what are some roles of protein phosphatases
- removing inhibitory phosphates from cyclin-Cdk complexes to activate them
- reverse downstream effects of Cdks by removing phosphates that Cdks add to their targets
are protein phosphatases regulated
- yes
- including by cyclin-Cdk complexes
what is used in the cell cycle to pause the cycle in various ways
- inhibitor proteins
- phosphate regulation
- cyclin regulation
what happens if the environment is not favourable for the cell cycle
Cdk inhibitors block entry into cell cycle
what happens if DNA replication is not complete
inhibition of activating phosphatase Cdc25 blocks entry to mitosis
what happens if there is DNA damage
inhibition of activating phosphatase Cdc25 blocks entry to mitosis
what happens if chromosomes are not properly attached to the spindle
inhibition of APC/C activation delays completion of mitosis
are Cdks stable or unstable in early g1 phase
stably inactive
what happens when conditions are suitable in g1 phase
the cell can transition into S-phase and through the rest of the cell cyclel
what happens when conditions are not suitable in G1 phase
- cell-cycle machinery can transiently hold the cell in G1
- or enter a more prolonged nonproliferative state G0
what happens to the machinery active in late M phase as the cell re-enters G1 phase
must be inactivated
what do mitogens do
activate signaling pathways that stimulate the synthesis of cyclins and other proteins involved in DNA synthesis/ chromosome duplication
what does accululation of cyclins synthesized by mitogens do
will lead to G1/S-Cdk activity to allow progress into S phase
some cells will only divide upon stimulation from extraceullular signals called what
mitogens
what happens in G1 when there is DNA damage
- leads to an increase in [ ] and activity of p53, a transcription regulator
- p53 then activates transcription of a protein called p21- Cdk inhibitor
- p21 prevents entry into S phase and allows time for DNA repair before replication
how ong can cells delay cell cycle progression
temporarily or permanently
when do many cells in the human body stop dividing
once they differentiate
what happens to many cells in the human body once they differentiate
- stop dividing
- dismantle the cell cycle control system
what happens when cells enter G0
- are in an arrested state
- retain the ability to reassemble the cell cycle control system
what phase does DNA replication happen in
S phase
what happens in S phase
DNA is replicated w extreme accuracy to prevent mutations
how many times is the genome duplicated and why
- only once
- to prevent damage from gene amplification
where does preparation for DNA replication begin
early g1
what happens in early g1 regarding DNA
- chromosome configuration
- origin recognition complexes recruit Cdc6 to that helicase can open the double strand
what happens in S phase regarding DNA replication
- DNA helicase is activated
- promotes recruitment of the proteins involved in DNA synthesis
- prevents re-replication by phosphorylating Cdc6 and the origin recognition complexes
what happens if DNA replication is incomplete
entry into M phase will be delayed
what happens during G2 phase
cell continues to grow and prepare for M phase
what happens regarding M-Cdk complexes during g2 phase
- they accumulate throughout G2
- are not active until the end of G2 to help transition into M phase
what happens in late G2 phase
- the phosphatase Cdc25 removes inhibitory phosphates to activate M-Cdks which in turn indirectly activates more Cdc25
- active M-Cdk complexes suppress inhibitory kinases
- M-Cdks also turn on APC/C
what happens when M-Cdks turn on APC/C in late G2 phase
eventually directs the degredation of M-cyclin, inactivation of M-Cdks, and exit from M phase
what happens during interphase
- cell size increases
- chromosomes are replicated
- centrosome is duplicated
what are the two phases of M phase
- mitosis nuclear division
- cytokenesis cytoplasmic division
what are the stages of mitosis
- prophase
- prometaphase
- metaphase
- anaphase
- telophase
what happens during prophase
- duplicated chromosomes condense in the nucleus
- mitotic spindle assembles between the 2 centrosomes
- centrosomes begin to move apart
what is required to ensure duplicated chromosomes are properly segregated during mitosis
- cohesins
- condensins
what do cohesins do
assemble along DNA as it is replicated to hold sister chromatids together
what do condensins do
reorganize and condense each sister chromatid into discreet structures
what happens during chromosome condensation
- cohesion rings are partially removed
- this alows the sisters to remain associated but safely pull apart in later mitosis
after chromosome condensation, what assembles
- mitotic spindle
- contractile ring
what is the mitotic spindle composed of and what does it do
- comprised of microtubules and associated proteins
- pulls duplicated chromosomes apart
what is the contractile ring composed of and what does it do
- comprised of actin and myosin filaments around the equator
- splits the cell in 2
when does centrosome duplication occur
- begins in S phase
- completed by the end of G2 phase
what is centrosome duplication initiated by
- same Cdks that initiate DNA replication
when are the poles of the mitotic spindle formed
- prophase
- two centrosomes move to opposite sides of the nucleus
what is radiated out of the centrosome
an array of microtubules called an aster
what happens during prometaphase
- phosphorylation of nuclear pores and lamina
- breakdown of the nuclear envelope into small membrane vesicles
- chromosomes attach to spindle microtubules and undergo active movement
what prevents the spindle microtubules from making contact with the chromosomes in prophase
the nuclear envelope
what happens once the nuclear envelope breaks down in prometaphase
microtubules attach to the chromosome at the kinetochores
when do kinetochores assemble at the centromere
prophase
where are kinetochores located on sister chromatids
- each chromatid has one
- they face in opposite directions
what happens once the microtubules attach to the kinetochores
- the chromosomes are oriented under tension
- which signals that they are ready to be separated
when does dynamic instability rises and why
- at the start of mitosis
- partially due to M-Cdk mediated phosphorylation of proteins that influence microtubule stability
what are 3 kinda of microtubules
- astral
- interpolar
- kinetochore
what do astral microtubules do
position the centrosomes at the poles via attachment to the cell cortex
what are interpolar (non kinetochore)
- microtubules in a constant state of flux
- form the basic framework of the mitotic spindle along w associated proteins
what do kinetochore microtubules do
encounter and attach to the chromosomes
what happens during metaphase
- chromosomes align at the equator
- kinetochore microtubules keep each chromosome under tension from attachment at opposite poles
what happens during anaphase
- sister chromatids separate and are pulled towards poles
- kinetochore microtubules get shorter, and the spindle pores move apart contributing to segregation
when are cohesions broken down and why
- start of anaphase
- allows the sisters to be pulled apart
what allows cohesion linkages to be degraded
- protease called separase
- held in an inactive state by inhibtory protein called securin
- securin is degraded by APC/C so separase can be free to sever cohesion linkages
what happens to kinetochore microtubules when chromatids separate
they shorten via loss of tubulin subunits
what happens in anaphase A
- the sister chromatids are pulled toward opposite poles as the kinetochore microtubules depolymerize
- The force driving this movement is generated mainly at the kinetochore
what happens during anaphase B
- force between non-kinetochore microtubules from opposite poles…
- pushes and pulls the poles apart
what is the driving force in anaphase B
- kinesin act on overlapping non-kinetochore microtubules, sliding them past one another (push)
- dyneins anchored to the plasma membrane, move along the astral microtubules (pull)
what happens during telophase
- chromosomes arrive at poles
- new nuclear envelope forms around each set
- division of the cytoplasm begins w the assembly of the contractile ring
what happens once the chromosomes arrive at the poles
- vesicles of nuclear membrane surround the chromosome clusters and fuse to reform the nuclear envelope
- nuclear pores and lamina are dephosphorylated
what happens once the nuclear envelope is reformed
- nuclear pores restore the localization of cytosolic and nuclear components
- chromosome decondence
when does cytokinesis occur
- begins in anaphase
- is not completed until the 2 daughter nuclei have reformed in telophase
where does the plane of cleavage occur
perpendicular to the axis of the mitotic spindle
what is the contractile ring made up on
actin and myosin filaments
what divides a cell in 2
- sliding of actin against myosin generates the force
- as the ring contracts, it becomes smaller and eventually disassembles once the cell is split
how is the ER segregated during cell division
cut in 2 during cytokinesis
how is the golgi segregated in cell division
fragmented and distributed via motor proteins
how are mitochondria/ chloroplasts segregated in cell division
inherited randomly
how is the number of cells in a multicellular organism regulated
- rate of cell division
- rate of cell death
if cells are no longer needed, what happens
they enter programmed cell death (apoptosis)
what happens during development regarding toes and fingers
cells between them die
what happens when a cell dies of acute injury
- it releases their contents across their neighbours
- triggers a potentially damaging inflammatory response
what is cell necrosis
a cell dying of acute injury (typically accidental)
what is apoptosis
programmed/ intentional cell death
what happens when a cell dies of apoptosis
- cell collapses and the cell surface is altered to attract phagocytic cells- macrophages
- cell is engulfed before it can release its contents and trigger an inflammatory response
what is the difference between apoptosis and necrosis
- apoptosis intentional/ programmed death
- necrosis accidental
the molecular machinery responsible for apoptosis is what
a family of proteases called caspases
what are caspases used for
the molecular machinery responsible for apoptosis
which caspases work together to take a cell apart
- initiator caspases activate downstream
- executioner caspases dismember numerous key proteins in the cell
describe an example of caspases at work
degrade lamins to cause irreversible breakdown of the nuclear lamina which allows nucleases to enter the nucleus and degrade DNA
what are the main family of proteins that regulate the activation of caspases
members of the Bcl2 family
what do Bax and Bak do
- promote cell death
- by inducing the release of cytochrome c from the mitochondria to the cytosol
what are two members of the Bcl2 family that promote cell death
Bax and Bak
what members of the Bcl2 family prevent apoptosis and how
- others including Bcl2
- preventing the action of Bax and Bak
how can cell death be mediated by extracellular signals
- from neighbouring cells or the environment
- directly via cell surface receptors which trigger a caspase cascade
- or due to lack of extracellular signaling
