Chapter 18 Flashcards
four phases of the cell cycle
Interphase: G1, S, G2
M phase: mitosis and cytokinesis
mitosis
division of the nucleus
cytokinesis
division of the cell/cytoplasm
longest phase of cell cycle
interphase takes up most of the time
main characteristics of interphase
cells duplicate their content and grow in size, making proteins and organelles
in which phase does DNA get replicated
S (synthesis)
purpose of G1 and G2 phases
gap phases; cells monitor conditions and assess suitability for continued growth
G0 phase
cells can leave G1 and enter G0
cells become quiescent- not dividing or preparing to divide, but not dead
prolonged non proliferative state
some cells can re-enter G1
cell cycle checkpoints
set of regulatory proteins and processes that check to make sure previous steps are completed before moving on
three checkpoints in the cell cycle
G1/S- ensure favorable environment for growth
G2/M - ensures all DNA is replicated and not damaged
SAC - (spindle assembly) ensuresall chromosomes are correctly attached to mitotic spindle, happens in anaphase
CDKs
cyclin dependent kinases, control cell cycle checkpoints
regulated by phosphorylation/dephosphorylation
must bind to cyclin to become enzymatically active
cyclins
activate and direct CDKs to target proteins in cell cycle
concentration varies throughout cell cycle
active cyclin-CDK complex function
phosphorylates proteins required to initiate cell cycle
G1 cyclins
cyclin D; bond to CDK partners (cdk4, cdk6) in early G1 and form G1-CDKs to help drive the cell through G1 toward S phase
S cyclins, G1/S cyclins
cyclin A(s) and E(G1/S); bind to CDK partners (cdk2) in late G1 to form S-CDK and G1/S-CDK to trigger S phase
Cyclin M
cyclin B; binds to CDK partner (cdk1) in G2 to form M-CDK to trigger entry into M phase
cdks that each of the cyclins bind to
G1(D) -> 4 and 6
G1/S and S (E and A) -> 2
M (B) -> 1
does concentration of cyclin or CDK fluctuate to control cell cycle
cyclin, concentration of CDK stays the same but activity is regulated by concentration of cyclins
how are cyclin concentrations regulated
transcription and proteolysis (degradation)
how are S and M cyclins degraded
marked with polyubiquitin by anaphase-promoting complex (APC/C) or cyclosome
degraded by proteosome
drives transition from one phase to the next
(both concentrations drop about halfway through M phase)
effect of M cyclin degradation
M-cdk inactivation and leads the cell out of mitosis
cdc25
activating phosphatase; removes phosphates from cyclin-CDK complex to activate them (actives M-CDK allowing cell to enter M phase)
Wee 1
inhibitory kinase; adds phosphates to cyclin-cdk (M-CDK) complex to inhibit entry into M-phase
cell cycle inhibitors
pause or delay transition through cell cycle phases if the conditions are not favorable
p27
binds to active cyclin-Cdk complex and inhibits activity
cells in G1
metabolically active cells
growth and damage repair activity
which cells never leave G0
mature neurons and muscle cells
at what point do cells commit to division
G1-S transition
once DNA is replicated cell must split
mitogens
signal molecule that tells cells to promote cyclin production; switches on signaling pathways; stimulates G1 and G1/S cyclins
when are all cdks inactivated
by the end of M phase
ensures daughter cells don’t enter another division before going through G1
activity of G1 and G1/S CDKs
phosphorylate and activate Rb (retinoblastoma) proteins (transcription factors to transcribe genes for entry into S phase)
how does cell halt progression into S phase if DNA is damaged
DNA damage -> increase p53 concentration -> activates genes for cdk inhibitor p21 -> p21 binds G1-Cdk and G1/S-Cdk -> halts progression into S phase until damage is repaired
where does DNA damage cause the cell to arrest in
G1 (p53 causes inhibition of G1-Cdk and G1/S-cdk)
p53
transcription regulator produced when DNA is damaged to induce transcription of p21
p21
Cdk inhibitor protein that binds to G1-cdk and G1/S-cdk
ORC
Origin recognition complex; stays bound to origins of replication throughout the cell cycle
progression of ORC throughout cell cycle
early G1: cdc6 binds to ORC -> Helicase binds and cdc6 dissociates (pre-replicative complex) -> at the start of S-phase, S-Cdk triggers DNA replication by recruiting replication machinery
how does cell prevent replicating the same DNA twice
S-Cdk phosphorylates cdc6 and the ORC preventing replication occurring again at the same origin of replication
when does M-cdk start accumulating
G2
how is M-cdk activated
M-cyclin binds to cdk to form inactive M-cdk
cdc25 (phosphatase) dephosphorylates inactive M-Cdk
feedback pathways of active M-Cdk
active M-cdk phosphorylates and activates cdc25 (positive feedback)
and also activates APC/C complex for its own degradation to turn itself off
how does the cell prevent the progression of cell cycle into m phase if DNA replication is not done properly
cdc25 remains inactive if DNA is not replicated properly and M-Cdk remains inactive
following replication, what does the genome look like
each chromosome consists of 2 sister chromatids held together by cohesin rings (broken late in mitosis)
aneuploidy
chromosome segregations errors, usually as a result of defects in cohesins
condensins
protein complexes that carry out chromosome condensation early in mitosis
ring like structures that loop DNA into tight chromosomes
assemble on each individual sister chromatid
what causes assembly of condensin into DNA
assembly of condensin complexes onto DNA triggered by M-Cdk phosphorylating condensin subunits
purpose of condensins and cohesins
ensure proper segregation of duplicated chromosomes
centromere
noncoding DNA that links 2 sister chromatids together before separation
six stages of M phase
Mitosis:
- prophase
- prometaphase
- metaphase
- anaphase
- telophase
Cytokinesis (begins before mitosis ends)
centrosome
microtubule organizing center (where microtubules extend from)
when are centrosomes duplicated
as soon as DNA replication starts in S-phase
(triggered by G1/S-Cdks and S-Cdks)
completed by end of G2
duplicated centrosomes separation
separate at the beginning of M phase
separate to opposite poles of the dividing cell and make asters
microtubules of the two asters elongate and form bipolar mitotic spindle
asters
star shaped array of microtubules emanating from the centrosome
mitotic spindle
microtubule cytoskeletal structure that directs movement and separation of sister chromatids during mitosis
determines plane for cell division
contractile ring
cytoskeletal structure composed of actin and myosin filaments; contracts to divide cytoplasmic contents during cytokinesis
main characteristics of prophase
chromosomes condense
mitotic spindle assembles between two centrosomes (moving apart)
kinetochores start to assemble
main characteristics of prometaphase
breakdown of the nuclear envelope
chromosomes attach to spindle microtubules via kinetochores, start to undergo active movement
two spindle poles
kinetochore microtubules
microtubules that connect to chromosomes directly via kinetochores
kinetochores
protein complexes that hold two sister chromatids together at the centromere
assemble on condensed chromosomes in late prophase
connect the plus end of microtubules to centromere of sister chromatids (with connecting protein complexes)
non-kinetochore MTs
interpolar MTs; crosslink with opposite interpolar microtubules by interacting with motor proteins and other MT-associated proteins - stabilizes plus end and decreases depolymerization
Astral MTs
Mts that attach centrosome to cell cortex and forms spindle poles
short, radiate from centrosomes
main characteristics of metaphase
chromosomes aligned at the equator of the spindle (metaphase plate)
kinetochores of each sister chromatid attach to kinetochore Mts of opposite poles
main characteristics of anaphase
cohesin proteins cleaved (indirectly promoted by anaphase promoting complex (APC)
sister chromatids separate and pulled toward spindle poles
kinetochore MTs get shorter and spindle poles move apart
APC
anaphase promoting complex
indirectly triggers cleavage of cohesins by catalyzing ubiquitylation and destruction of securin, a protein that inhibits separase (proteolytic enzyme that cleaves cohesins)
- also targets M and S cyclins for destruction
anaphase A
kinetochore Mts shorten, pulls chromosomes poleward
anaphase B
interpolar MTs pushes poles apart, growth at plus ends creates sliding force to push poles apart
pulling force of the cell cortex and shortening of astral MTs pulls poles apart
telophase
two sets of chromosomes arrive at poles of spindle
new nuclear envelope starts to reassemble around each set
formation of two new nuclei marks end of mitosis
division of cytoplasm begins, assembly of contractile ring
cytokinesis
cytoplasm divided into 2 by contractile ring
pinches cell into two daughter cells
usually begins in anaphase but isn’t complete until two daughter nuclei form
disassembly of nuclear envelope
phosphorylation of nuclear pore proteins and lamins in prometaphase
assembly of nuclear envelope
dephosphorylation of nuclear pore proteins and lamins in telophase
when and where does PM furrowing appear
appears in anaphase at the plane perpendicular to long axis of mitotic spindle
cytokinesis in plant cells
new cell wall forms at the equator (cell plate) to divide cell at the start of telophase
phragmoplast formed by interpolar MTs and vesicles derived from Golgi guides process
apoptosis signaling cascade
activation of different caspases (suicide proteases)
- activated caspases can activate more procaspases, amplify proteolytic cascade
what triggers apoptosis
- initiator caspases are made as inactive procaspases (proenzymes)
apoptotic signal triggers assembly of adaptor proteins that bring together two initiator procaspases, cleave their protease domains to become active
apoptosis
controlled death of the cell by caspases
Bcl2
inhibits caspases and apoptosis
Bax/Bak
two death promoting members of Bcl2 family that activate caspases and apoptosis
death receptors
cell surface receptor proteins that induce apoptosis
anti-apoptosis survival factors
signal molecules that bind to cell surface receptors and activates transcription regulators that transcribes gene encoding Bcl2 - inhibits apoptosis
