Strand 4 - Cell cycle Flashcards
the cell cycle requires high…… to ensure stable inheritance?
fidelity
which 3 types of cells are found in the G0 phase?
terminally differentiated cells
quiescent cells
senescent cells
CDKs are protein kinases which transfer what group onto substrates?
a phosphate group
what are CDKs activated by?
cyclin proteins
what does APC/C trigger the degradation of?
M cyclin
give 2 examples of upstream kinases/phosphatases which are cdk regulators?
CAK and Cdc25
give an example of a CDK inhibitory protein
p27
APC/C signals to M cyclin to do what?
end mitosis and initiate cell division
APC/ is a …… ligase. It covalently attaches …… to M cyclin
ubiquitin ligase
attaches ubiquitin
what does SGF signal for the degredation of to promote G1-S transition?
degradation of CKIs
what does SGF attach to CKIs?
ubiquitin
what does mitogen promote the synthesis of?
G1-S cyclin
if there is DNA damage to the cell, what does the G2 checkpoint inhibit?
cyclin activity via CKIs
if a chromosome is detected as unattached by the M phase checkpoint, what is prevented?
M cyclin destruction
what drives the transition from G1 to S phase?
via activating which molecule?
active G1-CDK via mitogen activation
what does the G2 checkpoint check for?
if replication is complete, if DNA damage has been repaired, if cell is large enough,
what does the mitotic checkpoint check for?
if chromosomes are attached to spindle
if the M phase checkpoint is satisfied, which molecule is activated, causing the degredation of M-cyclin therefore?
APC/C
if checkpoints in the cell cycle cannot be satisfied cells can :
exit cell cycle terminally
start apoptosis
withdraw from cycle -> senescence
what does abherrant mitogen signalling cause to cells?
drives cells through the G1 checkpoint
what can defects in the mitotic checkpoint cause to chromosomes?
aneuploidy
which mutation causes cancer predisposition syndrome?
BubR1 mutation
which cell type have stopped proliferating?
nerve cells/neurons
which 2 receptors can mitogens bind to?
EGFR / HER2
when mitogens bind to either EGFR or HER2, which signalling cascade is triggered?
give an example of a gene this pathway causes to be activated
Ras - Raf - MapK pathway
Myc
Which cyclin gene does Myc upregulate?
which CDK can this cyclin gene then bind to and activate?
cyclin D gene
bind to CDK 4 / 6 (G1-CDK)
Which protein does G1-CDK target?
Retinoblastoma protein
which txn factor does retinoblastoma protein bind to?
E2F
which cyclins does E2F upregulate?
these cyclins can then bind to CDK2 to form what?
E and A
G1-S CDK and S-CDK
what do double stranded breaks in DNA activate, causing the **prevention of G1-CDK **progression into S phase?
ATM/R, Chk1/2
which CDK does p21, a CKI, inhibit?
G1/S-CDK
which cell structure is duplicated in S phase, as well as DNA?
centrosomes
do eukaryotes have one or multiple ORICs?
multiple
function of the SSBPs in DNA replication?
help strands separate
what does DNA primase do in replication?
initiates polymerisation
what do topoisomerisases do in replication?
remove supercoils
function of sliding clamp in DNA replication?
keeps polymerase on DNA
function of DNA ligase in replication?
joins okazaki fragments
telomeres are repeating units of what combo of bases?
GGGTTA
telomeres extend which end of a chromosome? 5’ or 3’?
3’
damaged DNA bases cause the helix to become what?
distorted
NHEJ is performed when what is detected?
DNA breaks
where is info used from to repair DNA breaks if the cell is in S or G2?
a sister chromosome
p53 inhibits which CDK?
M-CDK
which 2 types of division occur during meiosis?
reduction division then an equational division
during which phase of mitosis does the nuclear envelope begin to disappear?
prometaphase
during metaphase, what attaches to the sister chromatids?
microtubules
during ……. chromosomes condense?
prophase
during which phase of mitosis does the bi-orientation of the chromosomes on bipolar spindle occur?
metaphase
the contractile ring which starts to contract during telophase, is made up of which 2 components?
actin and myosin
entry to mitosis is driven by which CDK?
M-CDK
Which 2 downstream mitotic kinases does M-CDK regulate?
aurora and polo kinases
the kinetochore is the binding site on a chromosome for what?
microtubules
kinetochore proteins are recruited by which 2 kinases in early mitosis?
M-CDK and Aurora B
in prophase:
cohesin is……..
condensin is…..
cohesin removed (from chromosome arms)
condensin recruited
what is the function of cohesin molecules in prophase?
to hold 2 sister chromatids together
……… 1 and 2 co-operate to condense chromosomes in mitosis
condensins
microtubules are nucleated at which end?
minus end
microtubules can grow and shrink at which end?
the plus end
give an example of a nucleating protein in microtubules
y-TuRC
give an example of a microtubule adaptor protein (MAP)
Ndc80 or Nuf2
what are the 2 motors, allowing cell components to move along microtubules?
kinesin -5
dyenin
which ends of microtubules does kinesin walk to?
plus ends
which end of microtubules does dyenin walk to?
minus ends
what does kinesin-5 form which allows it to crosslink with microtubules?
dimers
which molecule moves kinetochores towards the cell equator?
CENP-E
which kinase detects bi-orientiation via detecting levels of tension (a mechanism not fully understood yet)?
aurora B
what does aurora B phosphorylate to remove microtubules from kinetochores?
Ndc80
what does the spindle checkpoint detect?
unattached kinetochores
which complex do unattached kinetochores produce, which inhibits APC/C, keeping the cell in mitosis?
MCC
which complex is no longer produced once all kinetochores are occupied with microtubules?
MCC
the coordinated degredation of which two molecules ensures that biochemical exit from mitosis and the onset of anaphase chromosome movements occur together?
M-cyclin and securin
during which phase of mitosis do condensins dissociate and cohesins re-associate?
telophase
which two things in normal stem cells, does asymmetric cell division balance?
proliferation and cell cycle termination
cell intrinsic ACD occurs in which type of cell?
neuroblast
cell extrinsic ACD occurs in which type of stem cell?
male germline stem cells
which two model organisms are ACD core mechanisms learned from?
c elegans and drosophila
polarization can be either microtubule or……. dependent?
RHO1
polarization in a drosophila neuroblast can be either from the …….. or the previous division
neuroectoderm
which group of proteins causes the polarisation of the c.elegans zygote?
PAR proteins
the positioning of mitotic spindle in all animals is controlled by the molecular machine, composed of which 3 molecules?
NUMA
LGN
Dyenin
which protein at the anterior side of the cell promotes the degradation of the germ plasm proteins, ensuring somatic specification?
MEX-5
Which protein directs the localization of staufen, prospero and brat?
miranda
what is an inhibitor of notch signalling?
numb
when protooncogenes are mutated, what do they mimic? what do they stimulate?
a stuck accelorator stiumulating abherrant cellular growth and division
what is the chromosomal instability linked with cancer?
aneuploidy
what happens to chromosomes following DNA ds breaks?
they are translocated or rearranged
what are the causes of aneuploidy in mitosis? (write out)
- inappropriate kinetochore-microtubule attachments
- compromised SAC
- centrosome overduplication
- problems with chromosome cohesion
- tetraploidy due to cytokinesis failure
aneuploidy occurs in which 3 cells?
hepatocytes, neural progenitors and neurons
how can cancer cells tolerate aneuploidy? (3 ways)
- lowering DNA damage response
- increase replication stress tolerance
- prolonged mitosis
which trisomy is associated with increased proliferation?
trisomy 12
in which type of cancer do trisomies confer a selective advantage upon stress such as hypoxia?
colorectal
which chimeric protein is the cause of chronic myeloid leukemia?
BCR-ABL
what happens to the protooncogene ABL when a cell is forced into the cell cycle?
it is aberrantly activated
name 3 agents which promote ds DNA breaks, increasing the risk of chromosome translocations in cancer
topoisomerase 2 poisons
radiation
CIN
ABL is associated with which chromosome in chronic myeloid leukemia?
9
BCR is associated with which chromosome in chronic myeloid leukemia?
22
what drug is used for the treatment of ABL (chronic myeloid leukemia)?
imatinib
the production of which protooncogene promotes cell proliferation and survival in BCR-ABL signalling?
MYC
the deletion and frameshift mutations that lead to loss of Rb function are observed in which type of tumours?
retinal
Rb inactivation predisposes patients to defects in which cell growth pathway?
p53
what are the 3 types of protooncogenes associated with the Rb pathway?
growth signals
Wnt
cytokines
what is Rb?
retinoblastoma = an eye tumour
what are the two types of retinoblastoma?
in which type of retinoblastoma are both eyes affected by tumours and the retinoblastoma is inherited?
sporadic and familial
familial = both eyes (high risk of other cancers)
through the transcription of what…..Rb leads to CIN and aneuploidy?
E2F
cancer cells have a high tolerance to what?
chromosome instabilities
