MCM Final Part 1 Flashcards Preview

MCM > MCM Final Part 1 > Flashcards

Flashcards in MCM Final Part 1 Deck (166):
1

LHON disease

Causes subacute loss of central vision in young adults (Mostly men)
Homoplasmic mutations in one of three genes for complex I
-NADH dehydrogenase 4 (ND4)
-ND6
-ND1
Retinal ganglion affected selectively
mitochondrial DNA

2

Leigh's Syndrome

More common in nuclear DNA
Mutations in complex I or IV
Developmental delay, respiratory abnormal, recurrent vomiting
Bilateral symmetrical lesions affecting mostly basal ganglia and brainstem

3

MELAS

mitochondria encephala, lactic acidosis, stroke like episodes
Fatal in childhood
Multisystem: brain, muscle, endocrine
Stroke-like episode due to infarcts in temporal and occipital lobes
antipathy
Mutation in tRNA Leu

4

MERRF

Myoclonus epilepsy and ragged red fibers
Mutation in tRNA Lys

5

RNAi

micro RNA is very small
folds back on self forms hairpin
Dicer cuts into small sections
splits into single strands
one digested and other binds to protein complex
miRNA protein complex prevents gene expression
degrades mRNA or blocks translation

6

LTR

identical sequences of DNA
Repeat hundreds of times
Found at either end of retrotransposons
formed by reverse transcriptase
Used by virus to insert genetic materia

7

Denotes starts of itnrons

GT

8

Denotes end of intron

AG

9

Helicase

unwinds DNA
breaks hydrogen bonds

10

Topoisomerase

Relieves over wound supercoils
Breaks phosphodiester bonds
Fluroquinolones can inhibit

11

DNA ligase

Seals nick between okazaki fragments

12

Polymerases

alpha- syn DNA RNA primer

13

SSBP

keep the DNA strands separate and straight

14

Arabinosyclyctosine

Nucleoside analog inhibitor
ara-C cytarbine
contains sugar arabinaose and converted to ara-CTP, inhibits DNA polymerase
Treatment for leukemia

15

Acycloguanosine

Acyclovir
Nucleoside analog inhibitor
herpes virus encoded thymine kinase phosphorylates acyclovir

16

Axidothymide (AZT)

used in HIV treatment
drug taken up an activated by viral reverse transcriptase

17

Ionizing

X rays
reactive oxygen species
can cause
-direct strand breaks
-base damage
-DNA protein cross links

18

Non ionizing

UV lights
covalent linkage between pyrimidine bases (T-T) and (C-T)

19

Spontaneous DNA damage

Depurination: purine base removed via hydrolysis of n-glycosidic bond --> apurinic or basic site

Deamination: amino group of purine or pryimidne hydrolyzed so that adenine converted to hypoxaniteh, guanine to xanthine and cytosine to uracil,

20

Thymine modification

methylated cytosine gets deaminated and changes to thymine.

G to T now

21

Intercalating

insert between stacked bases causes unwinding and separation of base pairs

BPDE

22

Xeroderma pigmentosum

Nucleotide excision repair
Photosensitivity
Melonmas

Uv of sunlight causes cyclobutane thymine dimers to form in DNA
-NER usually fixes

NER: chemical adults that distort DNA (dimers, adducts)

23

Hereditary nonpolyposis colorectal cancer

Mismatch excision repair (MER)
(Mismatched base in daughter strand)

24

BRACA

Recombination repair
non-homologous

BRCA1&2 tumor suppressor genes

25

Cockayne syndrome

TCR
Stalled RNA polymerase during transcription
photosensitivity premature aging

autosomal recessive, congenital disorder
mutant genes involved in TCR of DNA


Developmental and neurological delay, photosensitivity, premature aging

26

Direct repair

Thymine dimer corrected by photolyase

27

Base Excision repair

Altered bases detected by DNA glycosylase
Glycosylase removes bases
Ap endonuclease cuts phospho bond
AP lyase removes deoxyrib phos
DNA polymerase replaces nucleotide
Ligase seals

28

Nucleotide Excision Repair

recognizes distortions and nick DNA on both sides of damage site
- excision nucleas
DNA helices:removes stretch of DNA w/damage
DNA polymerase: fills in gap
DNA ligase: seals
Xeroderma

29

Mismatch excision repair

error in new strand
binding mismatch proofreading proteins
-MutS and MutL
Error causes bulge
HNCRC

30

Double strand break repair

non homologous: bring broken ends together and rejoins by DNA ligation one or more nucleotides lost
-BRACA

homologous

31

Transcription coupled repair

cells preferentially direct DNA repair to sequences that are actively being transcribed
RNA polymerase stalls at lesion and directs repair machinery there
Cockayne syndrome

32

Ataxia telangiectasis (ALT)

leukemia, lymphomya,
def ATM protein, a protein kinase activated by double stranded breaks

33

BRCA2

Breast ovarian cancer
repair by nonhomologous recombin

34

Ranconi anemia group

Congenital abnormalities, leukemia,
DNA inter strand cross-link repair

35

Start codon

AUG for Met

36

Sickle Cell anemia

missense mutation in 6th codon for gene for beta-globing
GAG --> to GTG
subs Val for a Glu
Causes to aggregate and form rigid rod like structures
Deforms RBC sickle cell shape
poor oxygen capcacity, clog capilaries

37

Duchenne muscular dystrophy

Large in frame and out of frame deletions to dystrophin one
OOF deletion: no expression dystrophin
-severe
-muscle wasting and wheel chair

In Frame: truncated forms of dystorphin
-milder form
-Becker muscular dystrophy
Muscles replaced with fat and fibroid

38

I-cell disease

deflected mannose 6P
can't tag lysomal proteins
high plasma levels of lysosomal enzymes

39

Aminoacyl tRNA steps

1) aminoacyl-rTNA synthetase catalyzes activation of AA by transferring AMP to COOH end of AA
- driven by ATP hydrolysis

2) transfers AA from AA-AMP to tRNA

40

Initaition

GTP bound initiator tRNA attached to P site of small SU (methionyl tRNA in euro)

Forms complex w/ mRNA strand AUG start codon and initating factors (IF and eIF)

Large SU added to form complex
-driven by hydrolysis of GTP

41

Streptomycin

binds to 30s SU prokaryotes to prevent assembly of initation complex

42

ELongatoin

activated AA attached to initation MET forms peptide bond

Second amincoacyl tRNA with GTP bound-elgonation factor binds to A site

GTP hydrolysis of elongation factor and release of factor
peptide bond formation between AA in A and P sites

catalyzed by peptide transferase

43

Prokaryotic elongation inhibitiors

tetracycline
chloramphenicol
clindamycin and erythromycin

44

Eukaryotic elongation inhibitors

Cycloheximide
Diphtheria toxin
Shiga toxin

45

Tetracycline

bind to 30S block entry of aminoacyl tRNA to ribosomal complex

46

Chloramephenico

inhibits peptide transferase can't form peptide bonds

47

Clindamycin adn erythromycin

Binds to large 50 s SU blocking translocation of ribosome

Erythromycin used to treat whooping cough

48

Cycloheximide

toxin inhibits peptide transferase

49

Diphtheria toxin

inactivated GTP bound Eegs interfering with ribosomal translocation

50

Shiga toxin and Ricin

binds to large 60S blocking entry of amino acyl tRNA to ribosomal complex

51

Puromycin

causes premature chain termination in both pro/euk
resembles 3' end of aminoacylated tRNA
enters A site and adds to growing chain
forms puromycylated chain and premature release

52

Termination

Triggered by stop codon in A site
-Release factor loaded to A site
-Triggers peptide transferase to cleave the ester bond between the C terminus of the chain and the tRNA

53

Cytoplasmic pathway

proteins destined for cytoplasm, mitochondria, nucleus or peroxisomes
Synthesis begins and ends on ribosomes in cytoplasm

54

Secretory pathway

Proteins destined for ER, lysosomes, secretion and membranes
First 20 AA of polypeptide chain contains a ER-targeting translocation signal

55

Translocation signal for nucleus

KKKRK signal sequence

56

Translocation signal for mitochondria

N-terminal hydrophobic alpha helix signal peptide

57

Translocation signal for membranes

N-terminal apolar region (stop-transfer sequence)

58

ER targeting signal peptide

1-2 basic AA (lys or Arg)
10-15 hydrophobic sequence

59

Secretory pathway translation on ER

1. signal recognition particle (SRP) wraps itself around ribosome-mRNA peptide complex
2. Tethering it to ER membrane, temporarily halts translation
3. Once protein directed into ER lumen, translation resumes and protein directed to luminal space
4. Enzymes on luminal side cleave the signal to release the protein

60

Sickle Cell anemia

eMutation in gene for human beta global alters conformation of HbA which causes it to aggregate and form rigid rod-like structures

61

Alzheimer's disease

mutation in gene for amyloid precursor protein (ARP) predisposes APP to misfiled and aggregate and form neuritic plaques in brain. Supplementation w/ lysine has recent clinical significance

62

Creutz-Jakob/ Kuru, Mad Cow disease

Prions are transmissible misfolded proteins that convert their properly folded host counterparts to the same misfiled structure that they possess

Brain tissue degenerates rapidly (tiny holes in brain)

63

Huntington disease

Mutation in the huntington gene results in expansion of CAG triplet repeats which results in a polyglutamine tract (Poly Q tract) resulting in an abnormal HTT protein (mHTT) mHTT forms intramolecular H bonds which eventually misfold and aggregate.

64

Parkinson disease

mutated alpha-synuclein aggregates to form insoluble fibrils characterized by Lewy bodies in disorders known as synucleinopathies.

Caused by N-terminal apolar sequence (functional form has alpha helix; fibril has insoluble beta sheets)

Results in neuronal death in the midbrain reducing the availability of dopamine

65

Glycosylation

Covalent bond to sugar residues

Glycoproteins either
- O-links: -OH of Ser or Thr-
-N- links: -NH of Asn (most common)

Occurs in ER where translated

Transferred by protein glycotransferase
Antibiotic Tunicamycin blocks this transfer

Over glycosylation leads to cataracts in eyes

66

Glycosylation steps

Precursor oligosaccharide (14 residue) is synthesized on membrane embedded dolichol (membrane tethered)

protein Glycotransferase transferred oligosaccharide to Asn

Hydrolyzing O-glycosidic linkage to glucose residue trims the branched mannose tree

67

Phosphorylation

Formation of ester bond between phosphate and OH of an amino acid

Phosphate removed by phosphatase

Phosphorylation regulates enzyme activity and protein function

68

Disulfide Bond Formation

Inter- and intra molecular disulfide bonds
Stabilize many proteins
These binds form between thiol (SH) group of 2 cysteine residues
Formation and reorganization of these bonds occurs in ER lumen
Faciliated by protein disulfide isomerases

69

Acetylation

N-terminus bonded to acetyl of long chain acyl residue
Thioesterifcation with a long chain acyl group

covalent linkage to amine
Residue affect Lys

70

Endocrine signaling

Signal (hormone) is transported via blood
-Epinephrine released by adrenal medulla acts on heart muscle
-long distance
-long lasting: half-life on minute scale
-Freely diffusing signals

71

Paracrine Signaling

Signal (paracrine factor) diffuses to neighboring target cell of a different cell type
-leydig cell synthesize and secrete testosterone induces spermatogenesis by acting of sertoli and germ cells
-local signaling
-short lived
-neurons

72

Autocrine Signaling

Secreting cells express surface receptors for signal
-or release to cells of the same type
-chemokines
-growth factors in cancer cells

73

Direct/ Juxtacrine SIgnaling

signal binds to signaling cell which then binds to receptor on the target cell (binds next door neighbor)
-Heparin-binding epithelial growth factor binds to EGF receptor
-Immune cells
Physical contact

74

Malnutrition effect on hormones

Increase glucagon release by pancreas
-promotes metabolism of glycogen
-inhibits glycogen synthesis
-increase blood glucose levels

Epinephrine
-stimulates glycogen metabolism by promoting glucagon secretion

If glycogen stores depleted
-corisol stimulated gluconeogenesis

75

Fed conditions effect on hormones

Insulin promotes glycogen synthesis
Stimulate glycolysis
Inhibits activity of gluconeogenesis

76

Deficiency in insulin

Leads to elevated blood glucose levels

77

Graves disease

Autoimmune disorder in which thyroid stimulating immunoglobin (TSI) bind to and overstimulates TSH receptors causing hyperthyroidism

Decrease TSH; increase T3/T4

78

Lipophillic signals
Lipophillic receptors

Lipophillic signals
-lipid soluble (hydrophobic) diffuse freely through membrane
-interact w/ receptors inside the cell
steroid hormones, thyroid hormones, retinoids
Must be bound to carrier protein to be transported through blood stream
Long half lives
Receptors in cytosol or nucleus

Oral contraceptives

79

Hydrophillic signals and receptors

Water soluble, cannot diffuse through membrane
Bind to surface receptors
Triggers activation/ inactive of down stream events
Shorter half lives
Receptors
-transmembrane proteins, undergo conformation change upon signal binding
-G protein coupled receptor, receptor tyrosine kinases

Drugs administer at time of need

80

GPCR Signaling

1. signalingmoelcules (ligands) bind to the ECD and cause conformational change
2. ICD activates its G protein by triggering exchange of GDP for GTP
3. Actived G protein interacts w/ membrane bound effector protein
4. Effector molecule catalyzes run the produces secondary molecules

81

Modulation of Adenylate Cyclase by Gs

Adenylate cyclase generates cAMP from ATP

cAMP activates PKA

Gs activation activates AC

82

Modulation of Adenylate Cyclase by Gi

Gi activation inhibits AC
from cAMP produced

83

Modulation of cGMP phosphodiesterase by Gt

cGMP DPE catalyzes hydrolysis of GMP to 5' GMP

Lowering concentration of cGMP causes hyperpolarization needed for vision

Light activated Gt which activates cGMP PDE

84

Modulation of cGMP phospholipase by Gq

Activation of Gq activates PLC which cleaves PIP2 into DAG and IP3
IP3 translocates to ER and opens ligand gates Ca2+ channels
Increase in Ca2+ causes translocation of PKC to plasma membrane which is activated by DAG

PKC phosphorylates Ser/Thr

85

Signal Desensitization

Ability to turn off or ignore a signal
1) hormone levels drop
2) remove the signaling molecule (phosphodiesterase will remove cAMP/cGMP)
3) receptor sequestration: endosome
4) receptor destruction: endosome + lysosomes

86

G protein receptor kinases (GRKs)

GRKs phosphorylates GPCR
Arrestin binds to phosphorylated GPCR at 3rd intracellular loop
Results Galpha-GDP does not get converted to GTP
Inactive GPCR

87

RTKs

receptor tyrosine kinase (RTKs)
- extracellular domain contains signaling molecule binding site
-signals tend to be growth factors
-single helix that spans membrane

88

RTKs signaling

1. signal binds to ECD, induces conformational change that causes dimerization of receptor
2. specific tyrosine are phosphorylized (autophosphorylation)
3. phosphotyrosine recognized and bound by adaptor and docking proteins (SH2 domain of Grb2)
-active downstream signaling pathways that are RAS dependent or independent
4. Triggers the phosphorylation of protein targets in the nucleus, plasma membrane, and cytoplasm; leads to alterations in gene transcription and protein activity

Ras-dependent signaling facilitated by mitogen activated protein kinase (MAPK family)

5. RTK signaling is terminated (Degradation of signaling molecules, ligand-induced endocytosis followed by lysosomal degradation, accelerated RAS inactivation, dephosphrylation

89

Nitric Oxide

No is produced in epithelial cells

NO diffuses to neighboring muscle and activates guanylate cyclase producing cGMP. cGMP does smooth muscle relaxation and vasodilation

Don't take w/ drugs that inhibit cGMP PDE
combination can lead to extreme vasodilation and fatal drops in blood pressure

90

Albuterol

is a beta-agonist and hydrophilic molecules
Binds to and activates beta-andrenergic receptors

Administered directly to the lungs (inhaler) to treat asthma, bronchitis

Beta-agonists relax bronchial smooth muscle and stimulate heart muscle contraction

91

Antihistamines

histamines, the allergy causing signaling molecule derived from histidine, bind to 4 histidine in GPCR

Antihistamines block histamine binding to GPCR, preventing allergic response

Other antihistamines that only bind to H1 receptor can act as anti-emetics and inhibit symptoms of motion sickness

92

Cholera

consumption of contaminated water
prevents inactivation of Gs-alpha

Covalent modification of alpha subunit ADP ribosylation of Arg, decrease GTPase activity

Gs-alpha remains active and continuously stimulates adenylate cyclase resulting in over production of cAMP

cAMP in intestinal cells opens cl channels, loss of water --> diarrhea

93

Pertussis (whooping cough)

Prevents activation of Gi-alpha
ADP ribosylation of lys of Gi-alpha prevents activation and dissocation of alpha subunit from the G protein complex

Less inhibition of AC and over production cAMP

94

Men of H20 secretion

Toxin activates AC to produce cAMP
cAMP activates CFTR
Leads to secretion cl-
build up negative potential across membrane
Leads to secretion of Na --> results in net secretion NaCL
Nacl build up and osmotic gradient across membrane --> water secretion

95

Insulin signaling via RTK

Insulin binds with scaffold including IRS-1
Bindings either GRB2 (Ras-dep) or PI3kinase (RAS-indep)
GRBS--> alters gene transcription
PI3kinase --> alters protein & enzymes
(PKB involved)

96

JAK-STAT receptors

a more direct route for affecting transcription
1. receptors bind cytokines, dimerize and bind JAKs
2. JAKs phosphorylate eacht over and the receptor
3. Receptor binds and phosphorylates STATs
4. Stats dissociate from receptor dimerize translocate to nucleus

97

Uniparental disomy

phenomenon when individual receive two copies of a chromosome or part of a chromosome from one parent and no copies form other parent. Can be random error in meiosis or occur in early fetal development. Often asymptomatic since since individual has at least one copy of gene

98

Genomic imprinting

certain genes are expressed only from the mother of the father. Imprinted alleles are silenced such that genes is expressed only from the non imprinted allele.

Imprinting is an epigenetic process that involves the methylation and histone modification of egg and sperm cells during formation

99

Permanent cell type

Remain in G0 phase
Cannot be regenereated
Cardiac muscle, neurons, RBC

100

Stable (quiescent) cell type

Retain ability to exit G0 and enter G1 when stimulated by growth factors
Ability to regenerate damaged tissues
Hepatocytes, epithelial cells

101

Labile cell type

never enter G0, are constantly dividing to replace cell populations
Gut epithelium, skin, hair follicles, bone marrow

102

Retinoblastoma

Hereditary: both eyes affected. Microdeletions in chromosome 13 RB gene
In hereditary one copy of RB mutated in every cell and cell becomes predisposed to become cancerous. If second copy gets damaged cells lose control of G1 checkpoint

Non hereditary: affects only 1 eye cells contain somatic mutations in two copies of RB gene

103

Genes

segments of DNA in a chromosome
each gene occupies a specific place, or locus

104

Chromatid

Is one of two identical copies of chromosome

105

Chromosome

identical sequences of one another that are linked together

106

Centromere

connects identical sister chromatid

107

Somatic cells

diploid cells that are differentiated

108

Gametes

are haploid

109

Homologous chromosome

Refers to pair of chromosomes
-2 copies each gene

110

Karyotype

entire set of a patients chromosomes

111

Mosaicism

Condition in which cells from a patient have different genotypes (& karyotypes)

Not all cells have the trisomy 21 or XXY etc but ONLY if this happens in mitosis. If nondisjunction happens in meiosis ALL cells have defect

Downs syndrome 46XX; 47XX +21
Klinefelter syndrome: 46XY; 47XXY
Turner syndrome 46XX 45XO

112

Lyonization

Natural mosaiscm inactivation of one X in females and it is random

113

Homologous recombination

creates a new combination of genes. A way to increase diversity in genes passed on through meiosis

114

Aneuploid

Cells w/ abnormal chromosome number
Trisomy 21

115

Robertsonian translocation

Abnormal occurs with acrocentric chromosome (Chr 14 and 21)

Acrocentric: centromere isn ot evenly in middle of chromosome

116

Prader Willi syndrome

genomic imprinting
deletion on chromosome 15, if paternal chromosome is deleted

117

Angelman syndrome

genomic imprinting
Deletion on chromosome 15, if material chromosome is deleted

118

locus heterogeneity

single disorder, trait or pattern caused by mutations in genes at different loci

119

pleiotropy

one gene creates two or more seemingly unrelated effects

120

Gene frequency

specify the proportion of each allele in a population

121

Genotype frequency

specify the proportion of each genotype in a population

122

Polygenic

traits in which variation is throught to be caused by the combined effects of multiple genes

123

Multifactoral

when environmental factors cause variation in trait

124

Recurrence risk is higher if

1. more than one family member is affected
2. expression of the disease in the proband is more severe
3. if probing is of the less commonly affected sex
4

125

Growing/ Interphase

G1: RNA & protein synthesis
S: DNA synthesis
G2: RNA & protein syntesis continues

126

Dividng/ Mitosis

M: chromosomes duplicate/ segragate
1. nuclear division (mitosis) at beginning
2. cell division (cytokinses) at end

127

Resting

Go: poor nutrients/ environmental condition
no growing / cell division

128

Restriction Point

Occurs in G1 phase before G1 check point
If Growth factors are limited restriction occurs
Two hrs prior to S phase

Once they pass this, the cells become growth factor independent and continue on

129

G1 checkpoint

Occurs in G1 (late) before S
Occurs in response to DNA damage

130

G2 check point

occurs at end G2 before M
verifies the completeness of genomic DNA replication before commiting to mitosis

131

M checkpoint

ensures chromosomes attached to mitotic spindle

132

Cell signaling the drives cell proliferation

1. Myc-TF that drive cell proliferation
2. Myc increases CDK levels
3. CDK phosphorylates RB
4. Pho-RB releases sequested E2F
5. E2F-TF drives cells from G1 to S

133

CDK actiavtion

binding of cyclin partially activates

CDK activating kinase (CAK) need to fully activate

134

CDK inhibition

CDK inhibitors (p27 and Wee1) inhibit the cyclin-CDK complex
inactivates the kinase activity of cyclin-CDK

135

CDK activation

1. T loop region of CDK blocks active site
2. cyclin binds, T loops moves out of active site
3. CAK phosphorylates T loop
4. fully activate enzyme

136

G1 cyclin (D)

helps the passage of cells through the restriction point in late G1 phase
CyclinD-CDK4
CyclinD-CDK6

137

G1/s cyclin (E)

helps cells at the end of G1 phase to commit to DNA replication and enter S phase
Cyclin E-CDK2

138

S phase cyclin (A)

Necessary for the initiation of DNA synthesis
Cyclin A-CDK2

139

M phase cyclin (A and B)

Necessary for nuclear division during mitosis
Cyclin A-CDK1
Cyclin B- CDK1

140

Wee1 kinase

inhibits CDK activity by phosphorylating roof sites

141

Cdc25

dephosphorylates roof site to increase CDK activity

142

CKI

CDK inhibitory proteins
called p27 binds to both cyclin and CDK
inactivates complex

143

Cyclin turnover

progression from metaphase to anaphase
key regulator: APC/C (called cyclosome)

cyclin-S and cyclin-M must be downregualted

1. APC/C activated by binding Cdc20
2. activated APC/C poly-ubiquinates its substrates
3. Leads to addition of polyubiquitin to S and M cyclin complex
4. Clycins targeted for destruction from proteosomes
5. CDK dephosphorylated (inactive) after cyclins degraded

144

p53

a E3 ubiquitin ligase (MDM2) keeps p53 inactive through degradation until DNA damage detected.

p53 phosphorylated and stabilized and activated
Leads to increase in transcription of specific CKI (p21)
Binding and inactivation of cyclin-CDK by p21 causes cell cycle arrest

145

Extrinsic pathway

Death receptor
FAS: is an external death ligand that binds to receptor onto plasma membrane
Then adaptor proteins contains death domain bind to intracellular region of activated receptor and recruit procaspase 8 --> cascade

146

Intrinsic Pathway

Mitochondrial
Triggered by growth factor withdrawal, DNA damage, lack O2, lack of nutrient, lack of external survival signals, cell cycle defects

Bax/Bcl proapoptotic proteins reside in outer mitochondria membrane
BAX self aggregates
Stressed mitochondria releases cytochrome Cyt C bind to adaptor protein APAF1 --> apoptosome which recruits procaspase 9 --> cascade

147

Breast Cancer

HER2 is a product of protooncogene

Point mutation changes Val to Glu converts HER2 into the oncoprotein NEU which dimerizes and tyrosine kinase activity is activated in absence of ligand

A point mutation resulting in oncoprotein over expression in many cancers

148

Glioblastoma

EGF is product of photo-oncogene
Deletion mutation changes EGF to constitutively active EGFRviii oncoprotein

149

Chronic myelogenous leukemia (CML)

a translocation between chromo 9 and 22 results in formation of der (22) philedelpha chromosome and leads to the production of the fused protein kinase BCR-ABL

150

Retinoblastoma

is a tumor suppressor

151

Hallmarks of cancer

1. self-sufficiency in growth signals
2. Evading growth suppressors
3. Activating invasion and metastasis
4. enabling replication immortality
5. inducible angiogenesis
6. resisting cell death

1. tumor cells show lack of necessity of growth factors because many oncogene products mimic growth signaling

152

Epstein Barr virus --> cancer

DNA virus
Burkitt lymphoma
Nasopharyngeal carcinoma

153

Hepatitis B virus --> cancer

DNA virus
liver cancer

154

Human papilloma virus (HPV)--> cancer

DNA virus
benign warts, cervical and uterine cancer

155

Human T cell leukemia virus type 1 --> cancer

RNA virus
Adult T cell leukemia/ lymphoma

156

Kaposi sarcoma-associated herpes virus

capos sarcoma

157

Alkylating agents

(affects all phases of cycle)

cyclophosphamide (mustard gas)

Blocks DNA replication

158

Antimetabolites

S phase

5-flurouracil, methotrexate

INhibit enzymes involved in DNA synthesis
(slow down tumor growth)

159

Topoisomerase II inhibitors

S phase

Etoposide, Teniposide

Inhibits topoisomerase II, an enzyme that resolves tangles in DNA

160

Cytotoxic antibiotics

S & G2 phase

daunorubicin, doxorubicin

intercalate between bases in DNA to inhibit DNA syntehsis

161

Topoisomerase I inhibitors

S, G2, M phase

topotecan

Inhibit topoisomerase I and enzymes that removes supercoils in DNA

162

Mitotic inhibitiors

M phase

docetaxel, paclitaxel

Arrest cells in mitosis during metaphase

163

Inhibitory antibodies that bind HER receptor

Perception
Work on both protooncogene and oncogene

Blocks dimerization of receptor by binding EC domain and drives tumor cell lysis selective and HER2 degradation

164

Blocks EGF receptor

Erbitux (cetuximab)

Blocks ligand binding to EGFR

165

Gleevec

ATP binding site fusion protein

Gleevec Bind BCR/ABL fusion protein and inhibits ATP, in absence you get leukemia


166

copy number variations

CGH arrays