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FOUNDATION OF MEDICINE 2020 :building_construction:, FIXING :hammer_and…
FOUNDATION OF MEDICINE 2020 :building_construction:
CHROMOSOME
(☞ﾟヮﾟ)☞☜(ﾟヮﾟ☜)
DNA 🧬
DNA MUTATION :face_with_head_bandage:
DNA damage checkpoint :heavy_check_mark:
turn off/ inhibition :no_entry:
Cdk activity terminated
proteasome-mediated cyclin
cyclin ubiquitination
ubiquitin ligase
CKI
slow cell cycle progression
arrest the cell in phase
G1 -- stop G1/S Cdk
G2 -- stop M Cdk
cell size checkpoint
mTOR
monitor
nutrients
level of AMP
increase CKI
when high AMP
when low nutrients
dsDNA break in interphase
p53
normally it's ubiquitinated
constantly made and destroyed
kinase -- p53 stop usual ubiquitination
first go to
high affinity
genes
p53-responsive CKI
arrest cell cycle
repair protein
continue repairing DNA
G0 + G1 : NHEJ
G2 + S : BRCA
too much damage
low affinity
genes
pro-apoptotic proteins
initiate cell death :
DNA DAMAGE to DNA SEQUENCE :broken_heart:
pol delta/epsilon 🙄
#
types
pol slip
sequence of short repeat
ssDNA loop
#
insert - if DNA pol slip on daughter strand
deletion - if DNA slip on parental strand
general error
nucleotide mismatch
#
NO stall DNA pol
hydrolysis = nitrites -> nitrous acid 😬
base deamination
#
#
stall DNA pol
cell metabolism
:shallow_pan_of_food:
type
base alkylation
#
#
- base oxidation
stall DNA pol
missing H bond
UV radiation :sunny:
cross link pyrimidine = DNA distortion
#
stall DNA pol
missing H bond
ionizing radiation
oxygen free radicals :factory:
ssDNA break
#
break phosphodiester bond
microorganisms
#
virus
HPV = cervical cancer
hep B and C = liver cancer / inflammation
bacteria helicobacter pylori
stomach cancer due to stomach ulcer
MALT lymphomas
DNA REPLCATION
initiation
assemble 2 replication fork at each origin
origin licensing :card_index:
pre-replication complex assemble - licensing
origin recognition complex bind origin sequence
cell cycle protein
mcm helicase binds at each end of the complex
G1/S Cdk -> increase S Cdk
maintain DNA replication enzyme
prevent repeated relicensing of origins
after first licensing, cell cycle protein ubiquitinated and degraded
DNA synthesis 🧬🧬
ENZYMES
HELICASE
open DNA helix
DNA POL
DNA pol delta
towards origin
read template strand 3'-5'
lagging strand
fragments
proof read
DNA pol epsilon
read template 3'-5'
away from origin
leading strand
continuous
proof read
NUCLEASE
removes RNA primer
PRIMASE
PRIMASE
short RNA primer
DNA pol alpha
add dNTPs
cannot synthesize long strand
LIGASE
join DNA fragments
CHROMATIN
DNA METHYLATION
during S and G2
original strand was methylated
during DNA rep, one strand is hemi methylated
DNA methylase maintenance recognize the hemi-methylated and methylate new
to maintain gene silencing
impriting differential expression of parental alleles
HISTONE TAIL MODIFICATION
unmarked nucleosome
maintenance enzyme spot the unmarked and mark them
during S and G2
termination
telomere synthesis :white_flag:
overview
dsDNA sequence
the
end of the chromosome
synthesized
RNA template
telomerase
T loop
ssDNA overhanging hybridize with internal repeats
enzyme
telomerase
TERT
synthesize DNA using RNA
adding to the 3' end
TERC
RNA template
primase/ pol alpha
synthesize 5' strand of the telomerase using 3' DNA strand as its template
OVERVIEW
double strand
10 bp/turn
deoxyribose
base
cytosine
adenosine
guanine
thymine
synthesis
DNA polymerase
synthesis direction: 3'-5'
Substrate: dNTPs
must attach to the 3'OH
NUCLEOTIDE STRUCTURE
5' PHOSPHATE
substrate for nucleic acid synthesis
polymerase
3' OH
substrate for polymerase to add next nucleotide
polymerase
2'
H
deoxyribonucleotide
substrate for DNA synthesis
OH
ribonucleotide
substrate for RNA synthesis
1' NITROGENOUS BASE
PURINE
ADENOSINE
GUANINE
PYRIMIDINE
THYMINE
CYTOSINE
deaminate to uracil
URACIL
SUPERCOIL :lock:
Topoisomerase :unlock:
relieve supercoil
topoisomerase I
active in all cell
nuclease cut 1 strand
enzyme allows strand to unwind
ligase patches up
topoisomerase II
active in dividing cells
target for chemotherapy
#
inhibit ligase
promote dsDNA break = cell death
nuclease = break dsDNA
enzyme helicase move thru the break
ligase patch up DNA
overview
formed by: DNA helix crossing over itself
from undertwisiting and overtwisting DNA during DNA replication
OVERVIEW
chromosome STRUCTURE
telomere
repeating sequence
protect chromosome end
replication origin
DNA replication
S phase
centromere
attachment point for mitotic spindle
in M phase
phases
interphase
euchromatin
less densely packed
has genes that are transcribed
transcription regulation
histone tail modification
unfold = decondensation "beads-on-a-string"
refold into stacked loops
heterochromatin
associated with
lamin protein
inner nuclear envelope
stacked loops
genes not transcribed
telomeres
centromeres
genes not expressed in given cell
mitotic
chromatin max condensed
maximally compacted loops
no nuclear envelope
CELL CYCLE :recycle:
PHASES
G1
key events
increase cell size
prepare origin for DNA rep
monitor
nutrients
DNA damage
11h
CDK
EGF --> G1 cyclin increase
G1 cyclin + G1 Cdk
G1 Cdk -> G1/S cyclin
G1/S Cdk -> S cyclin
#
S
Key events
DNA replication
generate 2 sister chromatids
8 hours
CDK
G1/S cyclin increase
G1/S cyclin + G1/S Cdk -> G1/S cyclin-Cdk-P-P (phosphatase removes P -> active Cdk)
the middle of the G1/S Cdk spike is the transition between G1/S
prevent repeated initiation
after first DNA synthesis initiation
S CDk tell cell cycle protein to be ubiquitinated -> degradation
G2
key events
check DNA damage
monitor final cell growth
4 h varied
Cdk
S cyclin is still here
S Cdk -> M cyclin
M
key events
loss of nuclear membrane
cytokinesis separate cell into 2 daughter cells
condense chromatin
1h
CDK
the peak of M Cdk is the transition between G2/M
G0
growth factor
increase G1 cyclin
G1 Cdk increase @ the same time
increase G1/S cyclin
initiate S phase
cell commit to replication
by increasing transcription
RNA
OVERVIEW
Structure
one strand
fold back on itself in short ds helical regions
sugar - ribose
base
adenosine
uracil
cytosine
guanine
synthesis
read DNA template 3'-5'
sysnthesize 5'-3/
substrate NTPs
must attach to 3'OH
TRANSCRIPTION
Types of RNA pols
RNA pol I
rRNA
RNA pol II
mRNA
RNA pol complex structure
P-CTD tail
capping factor
splicing factor
poly A factors
RNA pol itself
processing
capping
7-methylguanosine
function
protect mRNA from degradation
ribosome recognize 5' cap = translation
splicing introns
complex structure
spliceosome
snRNPs
intronn structure
begin with GU
end with AG
bpA (somewhere in middle)
what bind where
U1 bind 5' splice site
U2 bind bpA
process
adenine of bpA bind to 5' splice site = lariat creation
5' splice site attacks 3' splice site = lariat release
ALTERNATIVE SPLICING
negative splice factor
HIDE splice site from recognition
positive splice factor
enhance recognition of splice site
poly-A-tail
function
facilitate mRNA transport outside of nucleus
stabilize mRNA
circularizes mRNA = increase translation initiation
process
recognize signal: GT rich and AATAAA region
pol A factors move from P-CTD tail onto the region
recruit
2 more items...
miRNA
RISC complex binds mRNA-specific miRNA + release "passenger" RNA
function
bind to 3'UTR
promote rapid mRNA degradation
small RNAs
RNA pol III
5s RNA
tRNAs
Transcription factors
act synergistically (product greater than sum of parts)
recruit
coactivator
histone acetylation
corepressor
histone methylation
histone deacetylation
recognize motifs of NDA
likes to "sit" in major groove
ways to regulate TF activities
gene expression level
phosphorylation
ligand binding (hormones --> can help TF recruit other co-activitors)
nuclear translocation
ubiquintination
PROTEIN :couple:
protein folding
protein folded correctly :smiley:
protein folded correctly with help of heat-shock chaperone :smirk:
incompletely folded protein :confused:
tagged by ubiquitin ligase
digested by
proteasome
change in protein amt w/o changing mRNA transcription
protein aggregate (not fit in proteasome) :unamused:
translation initiation factor
eIF2
form pre-initiation complex with small ribosomal subunit
virus case: viral dsRNA --> eIF2 kinase --| eIF2 --> slow viral replication
eIF4 + mRNA = initiation complex at 5' end
translation termination
release factor cleave
polypeptide off tRNA
release tRNA from ribosome
TRANSPORT :truck:
INTRACELLULAR
protein transported without vessicles
nucleus
mitochondria
peroxisome
cotranslational import/ vesicular transport
rough ER
SECRETORY PATHWAY
protein folding
quality control
ERAD
UPR
protein traffic Golgi -- Endosome
vesicle budding and fusion
Exocytosis
CYTOSIS-take things into cell
ENDOCYTOSIS
Clathrin
internalized molecules
viral and toxin entry
tyrosine sorting signal
hypercholesterolemia
overview
lysosome
endosome/lysosome
receptor-mediated
transcytosis
autophagy
phagocytosis
chemotaxis
pseudopods
phagosomes
granules
CELL SIGNAL :phone:
cell-cell communication :female-singer:
endocrine
adrenaline
epinephrine
insulin
paracrine
EGF
histamine
neuronal
acetylcholine
contact dependent
delta
secreting cell
( ´･･)ﾉ(._.`)
steroid hormone
abundant in smooth ER
steroid synthesis
lipid droplet
cholesterol ester storage
#
peptide hormone
rich in organelles
for protein secretion
golgi
rough ER
secretion granules
cell surface RECEPTOR ლ(・ヮ・ლ)
enzyme-coupled receptor
Types
activated associated enzyme
built-in catalytic domain
families
RTK pathway (EGF)
1a. ligand bind
1b. - RTK receptor dimerize
autophosphorylation
signaling protein bind to phosphorylated tyrosines
2 more items...
EGFR pathway
Ras - MAPKKK (Raf) - MAPKK (MEK) - MAPK (ERK) =
mitogenic
PIP3-PI3k - Akt -
mTOR
= growth
PIP3-PI3k - Akt = survival
by inhibiting apoptosis
small G protein
Ras - cell proliferation
Rho - actin assembly
Rac - actin polymerization
Rab - vesicle targeting
Ran - nuclear transport
ARF - golgi vesicle coating and uncoating
JAK-STAT
TGF-beta
ion-channel coupled receptors
neurons
dendrites
receive signal
passively conducting decaying signal to axon hillock.
depolarization can have different size
depolarization has to cross membrane threshold
axon
regenerative signal
AP - all or nothing
always same size, amplitude
pre-synaptic terminal
AP arrives at the presynaptic terminal
activate voltage-dependent Ca++ channel
Ca++ mediated vessel fusion into the presynapse membrane
synapse
neurotransmitter released
post-synapse receptor opens
Na+ enters post-synaptic cell
vesicles recycle
ions channel types
ligand-gated
acetylcholine
glutamate
GABA
BZD
potentiation of GABA-operated Cl- channel
voltage-gated (during action potential)
sodium voltage-gated channel
closed - membrane at rest
open - membrane depolarize
inactivated = refractory period
voltage gate remains open
inactivation gate closed
potassium voltage-gated channel
closed - membrane at rest
open - membrane depolarize
repolarization
mechanically gated
rely on external stimuli
stretching, pulling
Nernst equation
membrane potential a cell will shift towards when ion channel opens
G protein-coupled receptor
family
Gq
phospholipase C cuts PIPs into
DAG --> PKC
IP3 - increase Ca2+
biological effect
increase intestinal cell secretion
relax smooth muscle
<-- Gs
|-- Gi
adenylyl cyclase
cAMP
cAMP --> PkA
1 more item...
increase secretion of intestinal gland cells
contract smooth muscle
G12
Rho EGFs
blood clotting factors
proliferation / metastasis
BIOLOGICAL MEMBRANE
☆
: .｡. o(≧▽≦)o .｡.:
☆
FUNCTION
general
import/ export molecules
capacity for movement/ expansion
receive info
transporters
passive transporter
for molecules
hydrophobic
small uncharged, polar molecule
types
simple diffusion
channel mediated
solute discriminated based on size and charge
unsturable
passive
uniport
GLUT4
glucose in
passive
transporter mediated
antiport
Na+/H+
direction
Na+ out
H+ in
energy
passive when intracellular pH is high
secondary active when ....
symport
Na +/ glucose
direction
Na+ in
glucose in
energy
passive after carb rich meal
secondary active when limited glu
active transporter
requires energy
ions
voltage-gated
sodium voltage-gated channel
closed - membrane at rest
open - membrane depolarize
inactivated = refractory period
2 more items...
potassium voltage-gated channel
closed - membrane at rest
1 more item...
open - membrane depolarize
1 more item...
ligand-gated
acetylcholine
glutamate
GABA
BZD
potentiation of GABA-operated Cl- channel
mechanically gated
rely on external stimuli
stretching, pulling
large uncharged polar molecule
types
primary active transporter
Na+ K+ ATPase
3 Na+ out
2 K+ in
MDR transporter
excludes toxin
unregulated in
placenta
pt on chemo
secondary active transporter
symport
antiport
anchors
receptors
#
enzymes
2D fluid
protein surrounded by lipids
phospholipids
phosphatidylcholine
sphingomyelin
phosphatidyl protein (always on inner leaflet unless apoptosis)
phosphatidyl-ethanolamine
structure
plasma membrane
cholesterol
made at night
makes membrane more rigid
carbonhydrate
cell-cell recognition
blood antigens
protein
~100 lipid/protein
weight ratio 1:1
membrane proteins
transmembrane
alpha helices
beta barrels
monolayer associated protein
lipid-linked
protein attached -> driven by electrostatic
CELL DEATH :tired_face:
RELEASE OF CELL CONTENT
NECROPTOSIS
how?
cells round and swell
plasma membrane rupture
regulated
kill cell using reactive oxides
activate RIPK ---> MLKL
what?
no caspase
FAS, TNF R ligand
RIPK
MLKL
why?
when extrinsic apoptosis is blocked by inhibition of its caspase
self-induced necrosis
aftermath not discussed
PYROPTOSIS
б（＞ε＜）∂
how?
cell swells
plasma membrane disrupted
why?
intracellular infection
self-induced necrosis in response to bacteria
what?
non-apoptotic caspase
caspase-1 (different from caspases)
aftermath
intracellular hijack this to spread to new cells
SARS-CoV2
NET
OSIS
v(≧∇≦v)三(v≧∇≦)v
how
chromatin decondenses
cell expels chromatin NET and granule contents
where?
neutrophils
immune cell
why?
extracellular bacteria binding to receptors on neutrophil
also seen in autoimmune disease
what?
no caspase
sticky DNA
histones
aftermath
expelled DNA
neutrophils catch bacteria for other phagocytes to engulf and kill
NEUCROSIS
when?
not regulated
foreign pathologic
mechanical trauma
heat
radiation
ATP drop
disrupt membrane integrity
how
inflammation
cell volume increase
plasma membrane disrupted
DNA degraded
lysis
what? no caspase
aftermath?
ATP loss can prevent
regulated
forms of cell death
why? external stimuli
NO RELEASE OF CELL CONTENT
APOPTOSIS
༼ ༎ຶ ෴ ༎ຶ༽
why? cell suicide
EXTRINSIC PATHWAY
T killer cell with FAS ligand
activate death domain + death effector domain of FAS or TNF R
activate caspase
assemble DISC
aftermath
cytotoxic T cells express FAS ligand to help kill target cells expressing FAS
INTRINSIC PATHWAY
BCL2
bind to
BAK/BAX
BCL2 blocked = BAK/BAX free
BAK/BAX punch hole in mitochondria = release cytochrome C
activate caspase
form
apoptosome
(subunit arfg4)
internal stimuli
aftermath
BCl2 opposes activity of Bax/Bak to inhibit apoptosis and increase cell survival
how?
decrease cell volume
chromatin condensed
DNA cleaved
membrane intact, bleb
engulfed by phagocyte
no inflammation
what?
caspase cascade
initiator
executioner caspase
BAX/Bak,
BCL2 pro-apoptotic
apoptosome
when?
physiological damage
DNA damage
hypoxia
AUTOPHAGY
且_(・__・ )
why? cell eating itself for survival
--> initiation
low nutrients
high AMP/ATP ration
starving
hypoxia
ROS
infection
drugs
exercise
mTOR / EGFR --| initiation
what?
not caspase
AMP kinase
autophagosome
lysosome
how?
double-walled autophagosome engults particles/ organelles
lysosome fuse with atuophagosomes
aftermath
no cell death
CELL STRUCTURE
CYTOSKELETON MICROFILAMENT
INTERMEDIATE FILAMENTS
intermediate size
main function
structural integrity in cell with mechanical stress
work with desmosome for continuous network
no single monomer, several subunits
not polarized
associated protein
keratin
epithelial sheets
nuclear lamins
Damage = epidermis bullosa
MICROTUBULES
thickest size
main function
long-distance track for motor proteins
formation of mitotic spindle
neurons structure
monomers: tubulin heterodimers
alpha tubulin
beta tubulin
protofilament -> tubes of 13 protofilaments
polarized GTP
motor proteins
dyenin - towards cell body (-)
kinesins - towards axon (+)
associated cell components
centromeres
cilia
Flagella
ACTIN FILAMENT
main function
contraction of muscles
cleavage furrow
changes in cell shape
cell motility
actin monomer
ds helix
polarized (ATP)
motor protein:
myosin
= muscle
associated cell components
platelet
microvilli
small size
CONNECTIVE
FIBROUS PROTEINS
provide mechanical strength
basement membrane:
collage IV
loose connective tissue: fibrillar collagen (mixed types)
MULTI-ADHESIVE MATRIX PROTEINS
functions
cross-link ECM components
bind receptors
target for cell junctions
basement membrane:
laminins
loose connective tissues:
fibronectin
PROTEOGLYCANS
function
protein linked to negatively charged GAG
provide cushioning
basement membrane:
perlecan
loose connective tissue
hyaluronan
other proteoglycans
CELL JUNCTION
TIGHT JUNCTION
function
cell-to-cell stitching
seal, gate, fence
linker protein
transmebrane
occludins - structural
claudin - gating
#
cytoplasmic
zona occuldins
#
disease
clostridium perfin
back-leakage fluid into intestine
diarrhea
ADHERENS JUCTION
function
belt around similar cells
structural framework of building
regulate permeability
#
#
linker protein
transmembrane: cadherins
mediate adherens
mediate tight junction
cytoplasmic: beta-catenins
regulation/ disease
APC
normally beta-catenin specific ubiquitin ligase keeps level
low
high
level APC --> T-cell factor --> cell division --> cancer
anchor gang
HEMIDESMOSOME
EXCEPTION FOR CRAWLING CELL: no hemidesmosome
FOCAL ADHESIONS
transient connection to basement membrane for cell motility
linker protein
#
#
transmembrane: integrins
cytoplasmic
fibronectin
collagen
where?
fibroblasts
immune cell
spots/anchor cells to
basement membrane
with intermediate filament
transmembrane linker proteins
on cell - integrins connect with
#
on basement membrane -
laminins
connect with
#
DESMOSOME
spots/ anchor
cells
together with intermediate filament
#
linker protein
transmembrane:
desmogelins
cytoplasmic:
plaque protein
disease
pemphigus
: autoimmune
antibodies against desmogleins
#
GAP JUNCTION
channels for direct communication between cells
connexins
connexins
--> 2 connexons = 1 channel
regulation
small molecules
ions
caMP
aa
sugars
vitamins < 1.5 nm
channel closed
high Ca2+
low pH
where ?
nerves
smooth muscles
epithelia
FIXING :hammer_and_pick:
BER
enzyme
glycosylase - recognize
PARP - fix with complementary strand
accurate
ssDNA
MMR
enzyme/protein
MutS / MSH2
MutL
endonuclease
ligase
MSH dimer???
accurate
ssDNA
NER
enzyme
TC-NER monitor new DNA strand
GG-NER monitor entire genome
remove dimer
accurate
NHEJ
dsDNA break
not accurate - deletion
Ku dimer recognize
nuclease cleave broken end, ligase joins
HR
dsDNA break
need sister chromatid
enzyme
BRCA1 gene organize repair
ATM recognize
accurate
organelles
ER
Golgi
lysosome
nucleus
peroxisome
CANCER
:skull_and_crossbones:
OVERVIEW
TYPES
mutation
GERMLINE MUTATION
SOMATIC MUTATION
danger level
benign
localized
clean, clear edge
surgically removed
high chance of survival
malignant
spread to local and distant sites
nasty looking
hard to remove if metastasized
earlier death
RISK
SPORADIC
2 acquired mutation/ activated oncogene
multifactorial inheritance
shared environment
shared exposure
shared health behavior
clinical presentation
average age onset
single site of disease
no germline
INHERITED
1 inherited mutation + LOH with 2nd hit
strong influence, often same type of cancer
clinical presentation
younger age of onset
bilateral/ multifocal disease
multiple primary cancers
questionable phenotypes clues
skin
benign lesion
PHENOTYPES
NORMAL CELLS
reproduce/ stop at rigtht time
stick together in place
specialized/ mature
die if move to other part of body
CANCER CELLS
reproduce without obeying signals from neighbor cells
stick together, move together
no specialization/ no mature
do not die if they move to other part of body
DRIVER GENE
ONCOGENES
GAIN OF FUNCTION
proliferation
makes the protein constitutively active without enzyme binding
DOMINANT = 1 allele is sufficient
normal function
cell division
not undergo apoptosis
example
BCL2
cyclin D aka cyclin G1
EGFR
CANCER MOA
coding mutation = abnormal protein
regulatory mutation = excessive amt
translocation = novel
gene amplification = excessive amt
SOMATIC
TUMOR SUPPRESSORS
LOSS OF FUNCTION
= no break
RECESSIVE = both inactive allele
example
BRCA 1/2
p53
signal
telomere shortening
hypoxia
DNA damage
hyperproliferative signals
GOF
mTOR signaling
epigenetic modification
upregulation of PFGFRbeta, Myo10, Pla2g16
recycling of EGFR/integrin
activation of RhoA/ROCK signaling
mevalonate pathway
LOH
inherited cancer syndromes
Li fraumenia syndrome
normal function
encode for apoptosis
cell cycle arrest
senescence
CANCER MOA
FIRST HIT
point mutation
insertion
deletion
germline or somatic
SECOND HIT
epigenetic silencing
mutation
somatic recombination
loss and duplication
chromosomal loss
treatment targeted site
DNA POLYMERASE
nucleoside analog
it's like a fake nucleotide
base + ribose
stall DNA replication
DNA pol accept the fake nucleotide triphospate
P53 induce apoptosis
cytosine arabinoside (
AraC
)
#
instead of ribose -- use arabinose
cannot elongate because DNA pol cannot add to the 3' carbon
TOPO-2
in active cell
phase S, G2, M
inhibit ligase activity
endonuclease causes dsDNA
Etoposide
inhibit ligase
#
ciprofloxacin
--| DNA gyrase in bacteria
DNA gyrase = TOPO-2
Guanine
cisplastin
crosslink Gs
failed MMR
#
add large platinum adducts to guanines
Alkylating agents
add large adducts to guanine
loss of base
#
all cell:
X-ray (ionizing)
#
PROTEASOME
#
eg: bortezomib
inhibit proteasome
--> abnormal protein aggregate
--> apoptosis of cancer cell
RTK
cetuximab
#
antibodies block EGFR who expressed excessively
gefitinib, erlotinib
#
EGFR that are always active
MOLECULAR TESTS DETECT
protein made by cancer cells
circulating tumor markers
test type: protein staining
eg: cytokeratins, estrogen R (ER)
useful for
diagnosis
response
cell proteins
test type: blood test for tumor marker
eg: hCG, PSA
useful for
prognosis
monitoring
ideally, screening (but problematic)
alteration in cancer-associated genes
Recurrent somatic mutations in sporadic tumor
test type
FISH
translocation
gene amplification
DNA sequencing
gene mutation
eg: EGFR, Her2, B-Raf, P53, BRCA
useful for
prognosis
response
insight to CA mechanism
gene expression pattern
microarrays-patterns of mRNA expression
eg: breast cancer
useful for
prognosis
response (identify treatment)
when DNA pol stall :forbidden:
fork collapse
ssDNA break
dsDNA break
#
#
#
translesion pol Ku
TL pol ε
pyrimidine dimer
not abundant
TL pol ξ
abundant
required survive endogenous damage
bypass --> increase substitution mutation
abnormal H-Bond