Block 5 Flashcards
(255 cards)
1
Q
What happens during the oxidation of bases?
A
Generation of strand interruptions from reactive oxygen species
2
Q
What happens during G1 to proceed thru the cell cycle?
A
Growth factors induce expression of cyclin D. Cyclin D associates with CDK4/6 and they inactivate Rb
3
Q
What are the steps to extrinsic apoptosis?
A
- fas ligand on killer lymphocyte binds fas receptor (juxtacrine signaling) 2. oligomerization of receptor and recruitment of death domain with adaptor proteins. 3. adaptor proteins contain death effector domains that recruit and activate initiator procaspase 8 4. caspase 8 is cleaved and activates effector caspases
4
Q
What is the function of E2F in G1?
A
E2F induces expression of DNA replication enzymes, cyclin D, cyclin E, and cyclin A
4
Q
What causes HNPCC?
A
Mutations in MMR proteins MSH2/ MLH1
5
Q
What happens when JAK proteins are activated?
A
Create binding sites for STAT proteins
5
Q
How are origins of replication “licensed” during G1?
A
Sequential assembly of origin replication complex, CDC6, CDT1, and mcm helicases
5
Q
True or false: eukaryotic DNA polymerases have 5’ to 3’ exonuclease activity?
A
FALSE. Require 5’ flap endonucleases
5
Q
What mutagens cause missing bases?
A
acid and heat depurination
5
Q
What are the steps to autophagy?
A
autophagosome engulfs portions of the cytoplasm. Autophagosome becomes acidified and forms autolysosome
6
Q
How does AZT work?
A
T base analog for fighting HIV
7
Q
What is the function of DNA PKCs + ku 70/80 system?
A
Fix double strand breaks
8
Q
What is the unfolded protein response?
A
Triggering of apoptosis due to unfolded proteins in ER via caspase 12.
9
Q
Name and explain the two prokaryotic DNA replication models
A
- Theta model: DNA unwinds @ origin in replication bubble. Leading strand in direction of fork with lagging strand opposite 2. Rolling circle: continuous synthesis @ 3’ end and 5’ end displaced
9
Q
Why are telomeres needed?
A
At the end of chromosomes, there are no places for RNA primers to start the last Okazaki fragment
9
Q
What are the symptoms and causes of trichothiodystrophy?
A
Defects in NER cause light sensitivity, premature aging, ichtyosis, and sulfur-deficient brittle hair
9
Q
What is the function of BRCA2?
A
Regulates homologous recombination
9
Q
What types of tumor-suppressor proteins can be mutated in cancer?
A
receptors/ signal transducers in inhibiting cell cycle (TGF-B), cell cycle inhibitors, check-point control proteins (p53), pro-apoptotic proteins, DNA repair enzymes
10
Q
What are the functions of cyclins?
A
Regulate activity of CDKs and regulate substrates that CDKs can phosphorylate. Cyclin+ CDK = master regulators
10
Q
What happens during prophase?
A
Chromosome condensation (condensins) and spindle assembly begins
11
Q
What mutagens cause deletions/ insertions?
A
intercalating agents (Acridines)
11
Q
How does MMR know which strand is the parent strand?
A
Parent strands are methylated while new daughter strands have not had time to be mehtylated
12
Q
What is the function of cyclinE-CDK2 at the end of G1?
A
Fully activates E2F and assembles preinitiation complexes on chromosomes
12
Q
What is the effect of thermal disruption?
A
Due to elevated temperatures. Increases rate of depurination and single strand breaks.
12
What is the function of mismatch repair (MMR)?
Correction of mismatches of normal bases via NER and BER proteins
12
What is the function of non-homologous end joining?
"quick and dirty" end repair that causes DELETION of DNA or other mutations because it joins dissimilar DNA sequences.
13
What forms the apoptosome and what is its function?
Cytochrome C + Apaf 1. Cleave and activate procaspase 9
14
What is the function of phosphatidyl serine in apoptosis?
Normally is located on the inner leaflet. During apoptosis, i is flipped out to outer leaflet to provide signal for phagocytosis
15
What mutagens cause altered bases?
ionizing radiation and alkylating agents
16
What happens if there is sustained cyclin B expression in a cell?
Cell becomes quiescent
16
What percentage of breast cancer is inherited? What percent of those inherited cases are linked to BRCA1 or BRCA2?
5-10% inherited; 60-80% inherited cases linked to BRCA1/2
17
What are some features of Okazaki fragments?
1000-2000 NT in prokaryotes and 100-200 in eukaryotes. Synthesis of each fragment on the lagging strand begins @ the replication fork.
18
What happens when TGF-B binds the TGF-B receptor?
3 receptors oligomerize and phosphorylate Smad proteins to activate them, causing a conformational change.
19
How is p21 turned on and what pathways is it involved in?
Turned on via p53. Involved in DNA damage checkpoints
20
Describe Ras in its inactive state
Bound to GDP and usually bound to the membran
21
What medication is being used to treat CML?
Gleevac
22
What is Rbs function when it's active?
Rb is a tumor suppressor and binds E2F
22
What happens during telophase?
NE reforms and cytokinesis occurs.
22
What type of mutations is seen in oncogenes?
Gain of function
22
What is the effect of Ras mutations in cancer?
Reduction of GTPase activity so more of the protein is found in the GTP bound active form
23
What effect can epinephrine have on heart muscle?
epinephrine activates GPCR and GPCRs activate MAPK which can lead to cardiac hypertrophy.
25
What happens when a ligand binds the cytokine receptor?
JAK lip kinase is activated via phosphorylation
25
What is the relationship between cancer cells and stromal cells?
Cancer cells influences stroma and stromal cells influence tumor growth. Ex melanoma cells release PDGF to stimulate fibroblasts in stroma. Fibroblasts secrete IGF-2 survival factor
26
True or False: homologous DNA recombination occurs between dissimilar sequences?
FALSE: only occurs between highly similar sequences
27
What is the significance of the RTK pathway in small cell lung cancer?
Extracellular EGF receptors are cleaved and dimerize without ligand binding to be constituently active.
27
What are some properties of mesenchymal cells after EMT?
gain of fibroblast shape, motility, invasiveness, mesenchymal gene expression, protease secretion, vimentin expression, PDGF recetor expression, fibronectin expression, etc.
28
What cyclin accumulates at the end of G1?
cyclin E that will bind to CDK2
29
What is the function of recombination enzymes?
Recognize and bind inverted repeats in recombination sites to form synaptic complexes.
30
What are the steps to metastasis?
1. primary tumor formation 2. localized invasion 3. intravasation into blood stream/ lymph 4. transport thru circulation 5. arrest in microvessels of organs 6. extravasation 7. micrometastasis formation (needs good stroma) 8. colonization and formation of macrometastasis
31
What is the function of cyclin B in the M phase
Phosphorylates lamins, condensins, microtubule associated proteins, APC/C
32
What are the properties of prokaryotic DNA replication?
Semiconservative, bidirectional, one origin per chromosome, semidiscontinuous, RNA primed
32
What are the properties of eukaryotic DNA replication?
Semiconservative, bidirectional, multiple origins/ chromosome, semidiscontinuous, RNA primed, replication of telomeres, nucleosome assembly
32
How are mobile genetic elements related to brain function?
Can contribute to brain diversity, but are linked to schizophrenia
32
What enzymes fill in the gaps of BER?
DNA pol B fills in gap and ligase joins strand
32
How do the autophagy and apoptosis pathways cross-talk?
Formation of autolysosomes can block caspase activation or caspase activation can block autophagosomes
34
What is the function of Raf in the MAPK pathway?
Raf phosphorylates and activates MEK
35
What is the function of BRCA1 in relation to p53, Wee 1, and CDC 25?
BRCA1 is a scaffold protein that enhances p53 phosphorylation and stabilization during DNA-damage induced cell cycle checkpoints. Also regulates Wee1/ CDC25 in G2/M checkpoints.
36
What happens to Smad proteins after they are activated and undergo conformational change?
Smad proteins dimerize and enter the nucleus to bind DNA and NEGATIVELY regulate growth
38
What does B-catenin do if not degraded?
Associates with TCF and activates genes for gene expression in the nucleus
39
What is the effect of aflatoxin?
Procarcinogen that can form bulky adducts and cause DNA mutations
41
How is Rb inactivated?
Hyperphosphorylation by cyclin D-CDK4/6
42
What is the function of Ras in the RTK pathway?
Ras activates the Mitogen Activated Protein Kinase Pathway by activating Raf
43
How are CDKs activated?
Cyclin binds and causes a conformational change and ATP binding. Phosphorylation on T-loop is exposed so it can be phosphorylated by CAK.
44
What is the function of cdc6/ cdt1?
Recruited after ORC binds and recruit mcm2-7 helicases. They are phosphorylated by CDKs
45
What are the effects of radiation therapy?
double strand breaks and reactive oxidative species generation to induce apoptosis.
46
What are the effects of alkylating agents?
Prevent DNA synthesis and transcription via blocking DNA separation, induce mutations, cause inter & intrastrand ligations and DNA cross-links
47
How does overexpression of the cyclin D gene contribute to cancer?
cell becomes extremely sensitive to growth factors and pushes faster thru G1. (43% head and neck and 50% breast cancers)
48
Explain the disease mechanism in Chronic Myelogenous Leukemia (CML)
Chromosomal translocation where the abl kinase is fused to the bcr gene. Change in substrate specificity of abl kinase
50
What kind of binding domain does Grb2 have and what is its function in the RTK pathway?
Grb2 has SH3 domains to bind to SH2 and bind SOS
51
What happens to B-catenin in the absence of Wnt ligand?
Targeted to the destruction complex, phosphorylated, ubiquitinated, and degraded
52
What do dimerized STAT proteins do in the nucleus?
Bind DNA directly and activate transcription
53
What are the three methods of mutagenesis?
1. Endogenous/ spontaneous 2. Genetic defects 3. Exogenous mutations
54
What are the effects of intercalating agents?
Slide in between bases of the DNA duplex and disrupt replication and transcription. Usually have planar ring structure.
56
What is the significance of the Wnt pathway in colon cancer?
APC is usually mutated so it cannot form the destruction complex.
56
What comprises a "bead" of packed eukaryotic DNA?
8 histone proteins with 146 bp DNA
57
What is the function of the tau subunit in DNA polymerase III?
interacts with helicase and holds DNA polymerase subunits together
57
What is the function of ribonuclease H1?
Nuclease specific for RNA in RNA/ DNA hybrids to excise primers. Does NOT remove last ribonucleotide from initiator DNA
57
What are some outcomes of site-specific recombination?
gene/ DNA integration, excision, inversion
57
What does base excision repair fix?
Fixes only base (purine or pyrimidine)
57
What are the symptoms and causes of Xeroderma pigmentosum?
Hereditary defect in proteins for NER important for repair of UV-induced DNA damage. Symptoms: severe light sensitivity and increased skin cancer
58
Where was the Rb protein first found?
identified in patients with hereditary retinoblastoma and those cells were found to have lost both alleles of Rb
59
Which cyclins bind CDK2?
Both cyclin E and cyclin A. Direct CDK2 to different substrates
60
What is the effect of UV-A?
Causes free radical generation and INDIRECT DNA damage
61
How does Ras dissociate from Faf?
GTP hydrolysis
61
What happens when microtubule associated proteins are phosphorylated?
Form the mitotic spindle
61
What happens without the survival signal in anoikis?
AKT is not activated so BAD is not phosphorylated. BAD induces cytochrome C release and caspase 9 activation
62
What is the function of 6-mercaptopurine and 6-thioguanine?
Interfere with purine synthesis
63
What is the role of DnaC in prokaryotic DNA replication?
Helps to load DnaB helicase onto DNA
65
What happens during prometaphase?
Disassembly of the NE, complete spindle assembly, and chromosomes begin to assemble @ both poles
68
What is the common pathway for TGF-B and Cytokine signaling?
Activation of the receptor causes phosphorylation of proteins that can translocate to the nucleus and regulate gene txn. Less intermediate steps than RTK
69
True or false: mobile genetic elements require specific sequence homology?
FALSE: can insert into "any or many" DNA sequences
71
How do inhibitory smads block TGF-B expression?
They are induced by TGF-B (negative feedback loop) and block Smad phosphorylation.
72
What happens to STAT proteins when the bind to the JAK kinase?
STAT proteins dimerize via SH2 domains and translocate into the nucleus
73
In what step of cancer therapy are we most lacking?
Developing appropriate drugs and delivery in clinical studies
74
What are some examples of intercalating agents?
Actinomycin D, aflatoxins, echinomycin
75
What is the function of AP endouclease in BER?
removes sugar phosphate
76
What types of mutations activate NER?
Bulky lesions (ex. thymine dimers)
77
What happens during anaphase?
Physical separation of chromosomes, sister chromatids move to opposite poles, poles move apart.
78
What happens when C:G is deaminated?
Changed to T:A or C to T point mutation. Can't be repaired
79
How much of the genome is non-coding?
98%- 50% repeating sequences & 50% unique sequences
80
What is the function of Fen-1?
5' flap endonuclease that removes last ribonucleotide from initiator DNA
82
How does the SHP1 phosphatase terminate the cytokine signaling pathway?
Inactivates JAK by dephosphorylation
84
What is the R point in the G1 phase of the cell cycle?
Point at which cyclin D levels don't depend on growth factors
85
What is the function of DNA poly delta?
Matures okazaki fragments and has 3' to 5' exonuclease activity
85
What are the effects of effector caspases?
Cleave lamins, activate DNA fragmentation and DNAse, chromosome condensation, nuclear fragmentation, calcium influx, blebbing, formation of apoptotic bodies.
85
How are capillaries in tumors abnormal?
Larger in diameter, loose pericyte attachment, dead-end or double-back vessels, "leaky" gaps between endothelial cells = metastasis
86
What are SH2 and PTB?
Common binding domains in RTK signaling that bind to phosphorylated tyrosines in the RTK
88
How are RTK signals terminated?
Receptor down-regulation or phosphatases
88
What is the function of PCNA?
Sliding clamp processivity factor for polymerases delta and epsilon
89
What is the function of 5-fluorouracil?
Used to fight cancer by blocking thymidine synthesis
90
What is the function of RPA?
heterohexameric SSB
91
What happens when APC/C is targeted to securin?
Normally, securin blocks separase, so APC/C blocks securin so separase is active and chromosomes separate
92
What is the effect of ionizing radiation?
breaks in DNA strands
93
What is the clinical significance of the cytokine signaling pathway?
Cytokines are important for hematopoetic cell development and immune responses.
93
Describe the activation of the angiogenic switch in tumor cells (growth factors)
Hypoxia = activation of HIF1a txn factor (normally degraded) Expression of VEGF to stim endothelial cells and chemoattractants for migration of endothelial cells
95
What happens during metaphase?
Chromosomes are completely aligned and APC/C inhibits securin to free separase
95
What type of mutation is seen in tumor supressors?
Loss of function
96
What is involved in a transition mutation?
pyrimidine to pyrimidine or purine to purine switch
96
What is the function of BRCA1?
recruited to sites of DNA damage and double strand DNA breaks. Regulates homologous recombination and NHEJ
98
What is the function of cyclin A in DNA replication?
cyclina/CDK2 triggers DNA replication by recruiting mcm helicase and DNA polymerase. Also phosphorylates ORC for degredation
100
What is the CMG complex and when is it formed?
Cdc45, mcm2-7, GINS Formed during G1 and regulated by S phase kinases
101
What is the function of proteins in the p21 CIP family?
Bind cyclin-CDK complexes and block kinase activity = universal cyclin-CDK inhibitors
102
What are some of the changes in the ECM during invasion?
Focal adhesions (integrins); actin regulators (cytoskeleton); matrix metalloproteinases (breakdown ECM)
104
What did the Mendelsohn Stahl Experiment show?
DNA replication is semiconservative
105
What are the symptoms and causes of Cockayne's syndrome?
Defects in NER cause premature aging, light sensitivity, and face/ limb abnormalities.
106
What medication is being used to treat EGFR truncation mutations in non-small cell lung cancer?
EGFR tyrosine kinase inhibitor Gentifib
108
What protein recruits APC/C to cyclin B?
Cdh1
109
What type of recombination occurs in antibodies?
VDJ site-specific recombination used to create Igs and TCRs in lymphocytes.
111
How many times can an origin be licensed?
Only once per replication cycle
112
What is the function of the anaphase promoting complex/ cyclosome?
Ubiquitin ligase complex that targets anaphase inhibiters and cyclin B. Induces cytokinesis.
113
What kind of protein is Sos and what is its function in the RTK pathway?
Sos is a GEF for the Ras G-protein and exchanges GTP for GDP to activate Ras
114
What is the function of adapter proteins and RTK?
Adaptor proteins link receptor with downstream signaling proteins.
115
How are bases alkylated?
Usually by methylation
116
What is the E2F positive feedback loop?
E2F is freed by cyclin D and goes on to make more cyclin D to free more E2F
117
What protein recruits APC/C to anaphase inhibitor protein (securin?)
CDC 20
118
What is the major method of DNA transposon movement?
cut and paste transposition
119
True or False: some cells don't go through the mitotic cell cycle?
FALSE. All cells go through the cycle, but division depends on growth factors.
120
How do nalidixic acid and nofloxacim work?
Target bacterial DNA gyrase and inhibit DNA replication for UTIs
120
What is the function of Bid/ Bim (BH3 only proteins)
Stimulate pore formation (pro-apoptotic)
121
What antibody is being used to treat the HER2 mutated receptors?
Trastuzimab
122
How is the cytokine signaling pathway terminated?
1. SHP1 phosphatase 2. SOCS
123
What is the angiogenic switch?
Onset of angiogenesis that is a trigger for tumor expansion and invasivness
125
What are some examples of receptor cross-talk?
-RTK and cytokine receptors can activate second messangers (PLC and PKC) -Cytokine receptors can activate MAPK -Phos. tyrosines can provide binding sites for \>1 pathway.
126
What happens when condensins are phosphorylated?
Activation for chromosome condensation
127
What is the function of MLH1?
Cutting of mismatched DNA
128
What is necrosis and how is it different from apoptosis.
Extreme form of apoptosis with a breakdown of membrane integrity (cell swelling, PM collapse, inflammation)
131
What are the ORC sequences?
Binding sites for ORC. Rich in A-T so it's easy to unwind. Contains other binding sites for proteins to attract ORC
132
What happens when lamins are phosphorylated?
Phosphorylation causes the disruption of the lamin network for nuclear envelope disassembly
133
What types of chromosomal translocations can lead to oncogenes?
NHEJ, chimeric proteins with altered function, fusion with different promoters for over-expression
134
How does the SOCS pathway inhibit the cytokine pathway?
Negative feedback loop. -Blocks STATs from binding (via competitive binding @ SH2) -Inhibits JAK kinase -Promotes JAK degredation
134
How is DNA replication terminated in prokaryotes?
Tus protein binds to ter sequences and blocks helicase so replication fork is stalled
135
What is the survival pathway in anoikis?
Integrins activate PI3K that activates Akt. Akt phosphorylates BAD and keeps BAD from promoting apoptosis
136
What is a reperfusion injury caused by?
Injury due to restoration of blood flow and spreading of built up reactive oxidative species and nitric oxide. Causes more mitochondrial damage and necrosis.
137
What are the 5 stages of the cell cycle?
1. G0= quiescent 2. G1= commitment for division 3. S = DNA replication 4. G2= prep for mitosis 5. M= mitotic cycle
138
What are two examples of non-retroviral retrotransposons?
LINE: long interspaced elements (17%) SINES: short interspaced elements (~10%)
139
Which types of mutations would activate BER?
deamination, X rays, ROS, alkylating agents
141
What is the structure of the repeated unit in telomeres?
Hexameric GC rich repeats
141
How do DNA polymerases fix copying errors?
3' to 5' exonuclease activity
143
How do some antimalarial drugs function?
Target DNA polymerases and topoisomerase II
144
What are the three main types of chemotherapy?
1. Alkylating agents and platinum based drugs. 2. Anti-metabolites 3. Organic drugs and natural products
146
Which cyclins are present during G2/ M?
Cyclin A-CDK1, cyclin b-CDK1
147
What are the two ways TGF-B signals can be terminated?
1. Sno/ Ski proteins 2. Inhibitory smads
147
What is the function of the gamma complex in DNA polymerase III?
Clamp loader
148
What are the three ways bases can by hydrolyzed?
Depurination, depyrmidation, or deamination
149
What is nitrous acid produced by and what is its effect?
Produced by nitrates and nitrites. Nitrous acid stimulates deamination
150
How is meiotic recombination initiated?
Genetically programmed double strand DNA breaks
152
What is the function of Xeljanz?
JAK inhibitor for RA
153
What is the clinical significance of beta-arrestin?
Beta-arrestin is part of a cascade triggered by GPCRs that can recruit SRC (MAPKKKK) to activate the MAPK pathway.
154
What happens when there is loss of apoptotic response?
Malignant tumor
155
How are heteroduplexes formed?
single-strand filament invades into a homologous duplex DNA molecule and one of the strands is displaced as the DNA rotates.
157
What mutagen causes dimer formation?
UV-B
158
What is the function of the RecA protein?
Enables a DNA single strand to invade and pair with a homologous region of DNA double helix. Forms a filament on single stranded DNA
160
What is the function of RFC?
Brings in PCNA
161
Explain the MPF/ frog oocyte experiment.
Oocytes stuck in G2 could be stimulated to undergo mitosis if progesterone was added. Progesterone contained MPF = cyclin B
162
What is the function of tumor suppressor PAI-1?
PAI-1 is involved in regulation of ECM proteins
163
What happens to cyclin levels during S phase?
Cyclin E degraded an cyclin A complexes with CDK2
165
What is the significance of RTKs in breast cancer?
HER2 receptor has a V to G mutation which causes receptor dimerization and activation without ligand binding
166
What mutagens cause interstrand cross-links?
Psoralen derivatives, mitomycin C
168
What is the function of MEK in the MAPK pathway?
Kinase that phosphorylates MAPK
169
What is the function of Bad/ Bik (BH3 only) proteins?
Bind and inhibit anti-apoptotic Bcl proteins (pro-apoptotic)
170
What types of mutations lead to oncogenes?
1. point mutation/ deletion: loss of regulation 2. chromosomal translocation 3. amplification: abnormal replication/ over expression
171
What sorts of things make up the "tumor microenvironment?"
Hormones, cytokines, enzymes involved in breaking down ECM
172
What is the function of gyrase/ topoisomerase?
Relaxes supercoiled DNA
172
What is the function of DNA poly epsilon?
synthesis of the leading strand. has 3' to 5' exonuclease activity
173
What are 4 causes of double strand breaks?
1. Physiologic: VDJ recombination 2. Non-homologous end joining 3. Pathologic 4. Homology-directed repair
174
Explain the disease mechanism of chronic lymphoblastic leukemia
Chromosomal translocation results in the overexpression of bcl-2 to promote cell survival
176
What enzymes do retroviral retrotransposons use?
Reverse transcriptase and integrase
177
Which phase of the cell cycle is the only one to be influenced by growth factors?
G1
178
Describe the Frizzled receptor
7 transmembrane regions with LRP co-receptor
179
What happens if you lose transcription factor p53?
Inability to arrest cell cycle progression (thru p21 activation); loss of ability to induce DNA repair enzymes; loss of ability to induce apoptosis (thru activation of Bax)
181
What type of recombination does MRSA use?
site-specific recombination to gain strength and transfer resistance
182
What is exchanged in homologous DNA recombination?
Highly similar DNA sequences between two different DNA molecules
183
What are the 5 main types of DNA damages?
1. Oxidation of bases 2. Alkylation of bases 3. Hydrolysis of bases 4. Bulky adduct formation 5. Mismatch of bases
184
What happens when the Wnt ligand binds Frizzled?
Axin recruited away from the destruction complex and B-catenin is not degraded.
185
What happens during myocardial infarction with necrosis?
Cells undergo necrosis and release myocardial specific enzymes with levels correlating to amount of damage
186
What are the properties of cancer stem cells?
can self renew and may be inherently resistant to chemo- and radiation therapies due to slow division. Give rise to rapidly dividing cells
188
What is the effect of UV-B?
C-C or T-T pyrimidine dimers and DIRECT DNA damage
189
How does acyclovir work?
Stops RNA polymerase
190
What enzymes do DAN transposons use?
Transposase
191
What is the function of RAG1 and RAG2?
Recognize recombination signal sequences and induce DNA cleavage
192
What are some of the steps to the multistep model of cancer progression?
1. loss of APC 2. DNA hypomethylation 3. K-ras activation 4. loss of p53
193
What is the function of DNA polymerase I?
Removes RNA primer and adds DNA 5' to 3' exonuclease activity to remove primer (knick translation)
195
About how many mutations occur in a single human cell per day?
10^4-6
196
What is the function of the INK4 family including p15 and p16?
Specific cyclin D-CDK 4,6 inhibitors. p16 mutation is a predisposition to melanoma and can cause over-expression of cyclin D
197
How to sno and ski proteins terminate TGF-B signaling?
Bind smads and down regulate transcription.
198
How do cancer cells use telomerase?
Normally, telomerase is not active and telomeres are gradually lost with each cell cycle. Tumors over express telomerase to increase length of telomeres
199
Which cyclin is active during S phase?
Cyclin A-CDK2
201
What are the different effects of exogenous mutagens?
DNA mutations, DNA adducts, and DNA cross-linking
202
What causes Fragile X Mental Retardation?
Amplification and expansion of a single trinucleotide on the X chromosome
203
What are the 3 main classes of transposons?
1. DNA transposons 2. retroviral retrotransposons 3. non-retroviral retrotransposons (large portion of genome)
204
What diseases are associated with autophagy?
Huntington's, prion disease, cancer, aging, liver disease, heart disease, infection/ immunity
206
What is the function of DNA poly alpha?
makes primer on Okazaki fragments. NO 3'-5' exonuclease activity
208
What cellular factors control Wee1/ cdc25 activity?
Cell size and DNA repair pathways
209
What is the function of MSH2?
Recognition of mismatch
211
How is cyclin B regulated?
Wee1 kinase: inhibitory phosphate on Y15 Cdc25: removes inhibitory phosphate
212
How is Raf (MAPKKK) mutated in melanoma and how is it treated?
Activating mutation (V600E) treated with Vemurafenib mutant kinase inhibitor
213
True or false: the cytokine receptor is a kinase?
FALSE. the JAK protein bound to the receptor is a kinase, but not the receptor itself
215
What are the 3 general classes of DNA recombination?
1. Homologous 2. site-specific 3. DNA transposition
216
Explain how T-cell leukemia is related to growth factors
Cells overexpress IL-2 which is a T cell growth factor and the IL-2 receptor. Autocrine tumor cells that produce their own growth factors
217
What is involved in a transversion mutation?
Pyrimidine to purine
217
What are the steps to NER?
1. DNA damage recognition 2. local DNA unwinding 3. DNA strand dual incision 4. DNA repair synthesis and strand ligation 5. Successful DNA repair
218
What are the two ways cancer stem cells are thought to arise?
Normal cell undergoes mutations to become a stem cell. Normal stem cell becomes cancerous
220
True or false: lifespan is directly correlated to DNA repair activity?
TRUE
221
What types of genetic defects lead to increased cancer susceptibility?
Defects in endogenous DNA repair and detoxification machineries.
222
What two proteins make up the destruction complex?
APC and Axin
223
What ist he function of Bax/ Bak in apoptosis?
Pro=apoptotic. Dimerize and results in cytochrome C release via pore formation and ion transport
225
What is the function of PARP 1 or 2?
Recognizes single strand breaks, cuts up affected area, and recruits other proteins to fix break
226
What happens to MAPK when it is phosphorylated in the MAPK pathway?
MAPK dimerizes and translocates into the nucleus to phosphorylate txn factors for genes in cell growth and differentitation.
227
What enzymes do non-retroviral retrotransposons use?
Reverse transcriptase and endonuclease. Depend on cell providing transposase and integrase
229
What is autophagy?
can be prosurvival or prodeath where the cell is engulfed from within. Supplies cell with amino acids, energy, and old organelle turnover
231
What are the hallmarks of cancer?
1. Sustained proliferative signaling 2. Evading growth suppressors 3. Activating evasion and metastasis 4. Enabling replicative immortality (telomerase) 5. Inducing angiogenesis 6. Resisting cell death 7. Deregulating cellular energies 8. Genome instability and mutation 9. Avoiding immune destruction 10. tumor-promoting inflammation
232
What is the function of Dna2
Has helicase and nuclease activity. Aids in the removal of long flaps at Okazaki fragments
233
What does the binding of peptide/ proteinhormones do to RTK?
Ligand binding causes dimerization and autophosphorylation
234
What happens if there is a decreased production of p15?
p15 is an inhibitor of cyclin D-CDK4 complexes, so increased activity of cyclin D
235
What are the properties of local invasion of primary tumors?
Disruption of cell-cell adhesions and cell-ECM interactions. Use of "leaky" vessels and degredation of BM via invadopodia
236
What happens when A:T is deaminated?
Changed to C:G or A to G point mutation
237
When homologous recombination occur?
highest frequency in meiosis
238
What mutagens cause incorrect bases?
spontaneous deaminations
239
What controls the intrinsic apoptotic pathway?
Membrane permeability to ions causes release of cytochrome C
240
What is the function of ligase?
Seals knick in backbone with phosphodiester bond. 3' OH of final replacemnt to 5' P group
241
How are LINES related to hemophilia?
One form of hemophilia results from L1 element insertion into factor VIII
242
What is the function of myc and its role in cancer?
Txn factor activating cyclin D and E2F. Overexpressed in cancers (neuroblastomas and B-cell lymphomas)
243
What is the function of mismatch proofreading machinery in homologous recombination?
Prevents promiscuous recombination between poorly matched DNA sequences and can lead to gene conversion post DNA mismatch repair.
244
What is the role of DnaA in prokaryotic DNA replication?
binds to AT rich DnaA box sequence and melts DNA. Recruits DnaB helicase
245
What is the function of Bcl-2, Bcl-xL?
Anti-apoptotic. located in mitochondrial membrane and inhibit pro-apoptotic function
246
What is the function of ligase 1?
Ligates Okazaki fragments
247
What is the function of topoisomerase?
Relieves torsional strain. Causes knick in one backbone, which is fixed later
248
What is the function of DNA glycosylase in BER?
Scan DNA and flip damaged bases so they're recognized and removed
249
What are the two subunits to telomerase?
TERC: RNA component w/ RNA template TERT: reverse transcriptase activity
250
What is the function of primase?
Creates RNA primer for DNA poly III
251
What is anoikis?
Specialized apoptosis that occurs when cells detach from ECM and lose survival signal from integrins
252
What are the core enzymes of DNA polymerase III (prokaryotic)
alpha: 5'-3' polymerase E- 3'-5' exonuclease core assembly =\> chain elongation and proofreading
253
Which cyclins are present in G1?
Cyclin D-CDK4, Cyclin D-CDK6 and cyclin E-CDK2 towards the end
254
True or false: Site-specific recombination requires extensive lengths of highly similar sequences?
FALSE: site-specific doesn't require extensive sequence homology, just short recombination sites.
255
How are the intrinsic and extrinsic apoptotic pathways linked?
Activated caspase 8 from extrinsic apoptosis cleaves BID to activate intrinsic apoptosis
