cellular homeostasis & cancer Flashcards
6 DNA repair pathways
-direct reversal pathway
-mismatch repair pathway
-base excision repair
-nucleotide excision repair
-homologous recombination pathway
-non-homologous end joining (NHEJ) pathway
where does endogenous DNA damage occur
in active DNA participating in cellular activity like cell division (intracellular causes)
causes of exogenous DNA damage & 3 examples
environmental, physical, chemical agents
ex.
UV & ionizing radiation
alkylating agents
crosslinking agents
the two categories of DNA mismatch repair enzymes
MutS enzymes
MutL enzymes
MutS enzymes are associated with which DNA mismatch repair genes
MSH2
MSH3
MSH6
MutL enzymes are associated with which DNA mismatch repair genes
MLH1
MLH3
PMS1
PMS2
4 causes of cell cycle arrest
damaged DNA
unrepaired DNA
partially repaired DNA
cell size too small
(CDKs) stands for
cyclin dependent kinases
4 things that CDKs control in the cell cycle
DNA replication
transcription
chromatin remodeling
mRNA processing
CDK activation mechanism
CDKs inactive at baseline
->
activated when cyclins bind
->
cyclin/CDK complex modifies target proteins via phosphorylation during cell cycle
cyclin/CDK complexes are activated by _____
mitogens
cyclin/CDK complexes are inhibited by _____
the activation of cell cycle checkpoints (control points) in response to DNA damage
cyclin D
-active in what phase
-function & mechanism of action
G1 phase
promotes cell growth & entry into S phase by activating CDK4, CDK6
cyclin E
-active in what phase
-function
transition from G1 to S phase
activates CDK2 to initiate DNA replication
cyclin A
-active in what phase
-function
late S phase & G2 phase
regulates DNA replication & prepares cell for mitosis
cyclin B
-active in what phase
-function & mechanism of action
M phase
drives events of mitosis (spindle formation & chromosome alignment) by activating CDK1
growth factors are needed _____, and are NOT needed _____
needed during early G1 phase
NOT needed after the restriction point (late G1 phase)
each growth factor binds to _____
a specific cell-surface receptor with receptor tyrosine kinase (RTK) activity
how do growth factors drive the cell cycle
activate RTKS & downstream signaling pathways
->
which regulates cyclin/CDK complexes
what is a senescent cell
a cell that can no longer divide
main benefit of cell death
maintains tissue homeostasis
3 common types of cell death
apoptosis
necrosis
autophagy
apoptosis
-definition
-mechanism
-benefit of mechanism
“programmed cell death”
membrane blebbing -> cell shrinkage -> condensation of chromatin -> fragmentation of DNA -> apoptotic bodies -> dead cell rapidly engulfed by neighbors
absence of inflammation during cell death
necrosis
-definition
-mechanism
-consequence of mechanism
“non-programmed cell death”
cell swells -> plasma membrane ruptures -> lysis of cell -> damages surrounding tissue
presence of inflammation during cell death
aggressive tumors _____ via necrosis
die from the inside out
necrosis is associated with _____
increased dissemination of cancer cells
autophagy
-definition
-benefit for cell
“break down & reuse old cell parts”
autophagic vacuoles -> membrane blebbing -> increased lysosomal activity
helps cell survival & maintenance
in a late phase tumor, autophagy supports & enhances _____
tumor growth
in early stages of cancer, autophagy has _____, which _____
anti-metastatic / protective role
limits cancer necrosis & inflammation
ferroptosis
-definition
-mechanism
-2 features
-triggered by
iron-dependent cell death
via genetic changes in iron homeostasis & lipid peroxidation metabolism
increased membrane density & small mitochondria
triggered by accumulation of iron
ferroptosis plays a critical role in _____
tumor suppression (may also activate tumors but research unclear)
pyroptosis
-definition
-mechanism
-causes release of
-triggered by
caspase-dependent inflammatory cell death
NLRP3 activated -> caspase-1 perforates cell membrane (by forming nonselective pores) -> water influx -> cell swelling, membrane rupture, lysis & cell death
causes release of alarmins (DAMPs, S100 proteins) (proinflammatory signals)
triggered by infection
pyroptosis is both _____ & _____
a tumor promotor & tumor suppressor
necroptosis
-definition
-protein & substrate needed
caspase-independent “cellular suicide”
protein RIPK3 & substrate MLKL
necroptosis is a tumor _____
suppressor
which programmed necrosis cell death type has maintained mitochondrial integrity
pyroptosis
what are driver mutations
mutations that cause a selective growth advantage to somatic cells in their microenvironment
driver mutations drive the cell lineage to _____
cancer (promote cancer development)
driver mutations in the _____ gene, encoding the _____ protein, are found in a majority of cancers
TP53 gene
p53 protein
what types of genes do driver mutations occur in
driver genes
an example of driver genes
oncogenes
mutation mechanisms that lead to proto-oncogene activation
-coding mutation
-regulatory mutation
-translocation
-gene amplification
_____ or _____ contribute to oncogenesis
abnormal proteins
excessive amount of protein
what are proto-oncogenes
genes that normally regulate cell growth & proliferation, or help cells stay alive
what activates a proto-oncogene
mutation or presence of multiple copies of the proto-oncogene
what is an activated proto-oncogene called
oncogene
what is the “molecular basis of cancer”
oncogenes inducing cell transformation
what is epigenetics
the study of how environmental factors can cause cells to modify gene expression (WITHOUT changing the actual DNA sequence)
examples of epigenetic changes
acetylation
methylation
hypermethylation
phosphorylation
ubiquitylation
acetylation _____ gene expression; methylation _____ gene expression
acetylation increases gene expression
methylation decreases gene expression
epigenetic changes are _____; genetic changes are _____
epigenetic changes = reversible
genetic changes = irreversible
5 mechanisms that may promote tumorigenesis
-impaired DNA repair
-epigenetic modification
-chromosomal shattering
-impaired protein synthesis
-cell transformation
_____ is the underlying cause of tumorigenesis
mutation
mutation in proto-oncogene results in _____ and promotes _____
GOF
tumorigenesis
common oncogenes
MYC
RET
PDGFRA
MET
KIT
FLT3
EGFR
BRAF
common tumor suppressor genes
TP53
TGFRB2
RB1
PTEN
CHEK2
CDKN2A
BRCA1
BRCA2
APC
mutation in tumor suppressor gene results in _____ and promotes _____
LOF
tumorigenesis
