Unit 1 Flashcards
(151 cards)
1
Q
______ is an important precursor in the biosynthesis of Vitamin C, deficiency of which results in _______.
A
hydroxyproline; scurvy
2
Q
_______ (HDACs) _______ the N-termini of histones, which restores the _______ charge on _______ residues
A
Histone deacetylases; deacetylate; positive; lysine
3
Q
_______ acetylate _______ of histones, which neutralizes the _______ charge on _______ residues.
A
Histone acetyltransferases (HATS); N-termini; positive; lysine
4
Q
_______ competitively binds to bcr-abl, a _______, and inhibits its activity.
A
Gleevec; tyrosine kinase
5
Q
_______ induces eIF2A phosphorylation which inhibits ternary complex formation, thereby preventing initiation and translation globally
A
Interferon
6
Q
_______ is a blood thinner by inhibiting modification to produce _______
A
Warfarin (coumadin); gamma-carboxyglutamate
7
Q
_______ upregulates translation by binding to _______, which phosphorylates 4E-BP1, which can no longer bind 4E; 4E binds the Cap
A
Rapamycin; mTOR (mammalian target of Rapamycin)
8
Q
53BP binds during _____ phase and dissociates during ____ phase or ___ phase.
A
G1; S; G2
9
Q
Accumulation of purines of low solubility can help describe the symptoms of which two pathologies?
A
Lesch-Nyhan disease, gout
10
Q
Actinomycin and doxorubicin (Adriamycin) have what biochemical effect?
A
The intercalate with DNA and interfere with DNA function
11
Q
CDK2-cycE inhibits _______ protein which promotes cell division.
A
retinoblastoma
12
Q
CDK2-cycE inhibits retinoblastoma protein which _______ cell division.
A
promotes
13
Q
Chk1 and Chk2 are activated by _______; they then activate DNA repair and _____ cell cycle progression.
A
ATR/ATM; inhibit
14
Q
Cisplatin
A
This is an alkylating-like compound: it forms covalent adducts and inhibits transcription
15
Q
Defective Nucleotide Excision Repair mechanisms result in which two pathologies?
A
Cockayne’s Syndrome and Xeroderma Pigmentosum
16
Q
Define the function of hMLH and hMSH.
A
Enzymes involved in mismatch repair DNA repair mechanism
17
Q
Define the function of MutS and MutL.
A
Enzymes involved in mismatch repair DNA repair mechanism
18
Q
Describe the high energy bond types
A
thioester (C-S), phosphoanhydrides, P-N bonds, C-O-P bonds
19
Q
Dimethylnitrosamine, nitrogen mustard, and dimethylsulfide affects DNA in what way?
A
These are alkylating agents: they form covalent adducts that inhibit transcription
20
Q
Exome sequencing is useful in diagnosing diseases with ____ patterns of inheritance, such as _______.
A
Mendelian; Miller’s Syndrome
21
Q
Hepatitis A and C, HIV, and Polio cleave _____ to shut down cap-dependent translation
A
eIF4G
22
Q
How is the activity of Beta-catenin regulated?
A
GSK3 (with APC and Axin) phosphorylates Beta-catenin and targets it for degradation via ubiquitin-proteasome pathway; Wnt destabilizes the Axin/APC/GSK3 complex to allow beta-catenin to persist
23
Q
How is the activity of CREB regulated?
A
CREB (cAMP Response Element Binding protein) requires phosphorylation to be activated
24
Q
How is the activity of NF-AT regulated?
A
NF-AT is phosphorylated which blocks the NLS; Under high calcium conditions, calineurin dephosphorylated NF-AT and permits nuclear entry
25
How is the activity of Nf-kB regulated?
I-kB binds to Nf-kB and blocks the NLS; Phosphorylation of I-kB causes dissociation and permits nuclear entry
26
How is the activity of p53 regulated?
MDM2 binds to p53 and masks its activation domain and targets it for destruction; high levels of p53 activate transcription of MDM2
27
How is the activity of the glucocorticoid receptor regulated?
Hsp90 is bound preventing entry to nucleus; binding of a hormone causes dissociation from Hsp90 and permits nuclear entry
28
In _______, Ku recognizes the DSB and recruits DNA PK-cs.
Non-homologous End Joining (NHEJ)
29
In multiple myeloma, proteasome activity is _______.
high
30
In Non-homologous End Joining (NHEJ), _______ recognizes the DSB and recruits _______.
Ku; DNA PK-cs
31
Ink4 and Cip/Kip inhibit _______, which _______ cell cycle progression
CDKs; inhibits
32
Interferon induces _______ phosphorylation which inhibits ternary complex formation, thereby preventing initiation and translation globally
eIF2A
33
Interferon induces eIF2A phosphorylation which inhibits ternary complex formation, thereby preventing _______.
translation
34
Monoclonal ab infusion, bapineuzamab, solanezumab, and IVIg are strategies to…
Increase Beta-amyloid clearance
35
Name 3 pathologies associated with mutations of TFIIH.
Xeroderma Pigmentosum, Cockayne's Syndrome, and Trichothiodystrophy
36
Name 4 compounds that form covalent adducts with DNA to inhibit transcription
Dimethylnitrosamin, nitrogen mustard, dimethylsulfide, and cisplatin
37
Name 4 viruses that shut down cap-dependent translation?
Hepatitis A and C, HIV, and Polio
38
Name the cause of Fragile-X Syndrome and some of the clinical observations.
An increase in CGG repeats in the FMR gene; mental retardation, craniofacial defects, and macroorchidisim
39
Name the DNA-binding region category for the following DNA binding proteins: Androgen receptor, MyoD, Pit1, c-fos
Zn finger; Helix-loop-helix; Helix-turn-helix; bZIP
40
Name the DNA-binding region category for the following DNA binding proteins: c-fos, c-jun
Basic Leucine Zipper (bZIP)
41
Name the DNA-binding region category for the following DNA binding proteins: c-jun, Myf5, Msx
bZIP; Helix-loop-helix; helix-turn-helix
42
Name the DNA-binding region category for the following DNA binding proteins: estrogen receptor, androgen receptor, retinoic acid receptor
Zinc Finger
43
Name the DNA-binding region category for the following DNA binding proteins: Hox family, Pit1, Msx
Helix-turn-helix
44
Name the DNA-binding region category for the following DNA binding proteins: Hox family, retinoic acid receptor, Myogenin
Helix-turn-helix; Zn Finger; Helix-loop-helix
45
Name the DNA-binding region category for the following DNA binding proteins: MyoD, Myogenin, Myf5
Helix-loop-Helix
46
Name the homologs of MutS and MutL.
hMSH and hMLH
47
Name the three enzymes (in order) involved in installing the 5' cap
Triphosphatase; Guanylyltransferase; Guanine 7-methyltransferase
48
Name two ATP-dependent ATPases.
SWI and SNF
49
Name two classes of proteins that inhibit CDKs
Ink4 and Cip/Kip
50
Name two drugs that interfere with DNA function via intercalation
Actinomycin and doxorubicin (adriamycin)
51
Name two drugs that interfere with DNA function via topoisomerase inhibition.
Camptothecin and etoposide
52
Provide an example for each of the high energy bond types.
Acetyl CoA, Phosphoenolpyruvate, ATP, Creatine
53
Rad 17 senses damaged DNA, which activates the transducers _______, which activate the effectors _______, which inhibit _______.
ATR/ATM; p53/p21; CDKs
54
Rapamycin upregulates _______ by binding to mTOR (mammalian target of Rapamycin), which phosphorylates _______, which can no longer bind _______ --> _______ binds the Cap
translation; 4E-BP1; 4E; 4E
55
T/F Binding of the IRE is required for expression of ferritin.
F
56
T/F Binding of the IRE is required for expression of the transferrin receptor.
T
57
T/F HATs promote transcription.
T
58
T/F HDACs promote transcription.
F
59
What Alzheimer's treatment method seeks to increase glucose uptake and synaptogenesis?
Intranasal Insulin
60
What are the biochemical effects of etoposide and camptothecin?
They interfere with topoisomerase activity which results in irreparable breaks in DNA
61
What are the homologs of Hsp70/Hsp40?
DnaK/DnaJ
62
What are the names of the eukaryotic polymerases?
Polymerase delta (lagging) and Polymerase epsilon (leading)
63
What causes Lesch-Nyhan disease?
Accumulation of purines of low solubility
64
What chaperone uses ATP to fold proteins correctly?
GroES/GroEL
65
What drug can be used to inhibit HIV protease?
Crixivan
66
What drug can be used to reduce blood pressure?
Captopril
67
What drug is involved in inhibition of protein methylation and acetylation?
Verinostat
68
What drug is used to treat Chronic Myelogenous Leukemia (CML)?
Gleevec
69
What drug mimics the structure of an aminoacyl-tRNA to inhibit translation?
Puromycin
70
What drug prevents the binding of estrogen to the estrogen receptor?
Tamoxifen
71
What drug prevents transcription by blocking the RNA exit site?
Rifampicin
72
What enzyme is responsible for installation of the Poly A tail?
Polyadenylate Polymerase
73
What is an X-linked disorder that affects blood clotting
Hemophilia B Leyden
74
What is targetted for degradation by the Axin/APC/GSK3 complex?
Beta-catenin
75
What is the 3' splice site consensus sequence?
AG
76
What is the 5' splice site consensus sequence?
GU
77
What is the biochemical cause of CDG-1?
Defect in N-linked glycosylatio of Asn
78
What is the biochemical cause of craniosynosis?
A proline to histidine mutation in the MSX2 gene that leads to activation of suture closure genes
79
What is the biochemical cause of Hemophilia B Leyden?
Mutation in the Factor IX gene that interferes with the binding of transcriptional activators
80
What is the biochemical cause of Rubinstein-Taybi Syndrome?
Haploinsuffiency of CREB Binding Protein (CBP)
81
What is the biochemical consequence of haploinsufficiency of CBP?
CBP is an activator for many transcription processes and has HAT activity
82
What is the biochemical effect of a mutation in a binding domain of the androgen receptor?
Decreased response to androgens/Androgen Insensitivity Syndrome
83
What is the biochemical effect of puromycin?
It mimics aminoacyl-tRNA, (1) binds the active site of the ribosome, (2) is transferred to the growing polypeptide chain, and (3) prevents completion of translation
84
What is the biochemical effect of rapamycin?
Rapamycin upregulates translation by binding to mTOR (mammalian target of Rapamycin), which phosphorylates 4E-BP1, which can no longer bind 4E --> 4E binds the Cap
85
What is the biochemical function of BRCA2?
Sense double strand breaks in damaged DNA
86
What is the biochemical function of ferritin?
Sequesters excess iron
87
What is the biochemical function of Hsp70/Hsp40?
Prevent protein aggregation by binding to hydrophobic residues and transporting unfolded proteins across membranes
88
What is the biochemical function of Id?
Id heterodimerizes with bHLH domains and prevents binding of DNA binding proteins
89
What is the biochemical function of IRE-BPs?
When Fe is high, they bind to Fe; when Fe is low, they bind to IRE
90
What is the biochemical function of IRE?
IRE (Iron Response Element) is a region on RNA that may be bound by IRE-BPs and then influence the expression of ferritin and transferrin
91
What is the biochemical function of the transferrin receptor?
Transports transferrin/Iron into the cell
92
What is the biochemical significance of ApoE4?
ApoE4 is associated with an increase in Alzheimer's Disease by increasing amyloid deposition
93
What is the biochemical target of aminoglycosidases (Ex. Stretpomycin) and tetracyclines?
The ribosome
94
What is the biochemical target of macrolides (ex. erythromycin) and chloramphenicol?
The ribosome
95
What is the cause of Beta thalassemia?
Mutation in promoter region of Beta-gobin gene that results in decreased expression
96
What is the cause of Cockayne's Syndrome?
Defect in NER
97
What is the cause of Gamma-Delta-Beta thalassemia?
Deletion of Locus Control Region (LCR), which is required for transcription of genes in the cluster
98
What is the cause of thalassemia?
Inherited anemia due to deficiency of Beta-globin in erythroid cells
99
What is the cause of Xeroderma Pigmentosum?
Defect in NER
100
What is the clinical consequence of chromosomal translocations that form functional fusion proteins?
Hematopoietic malgnancy (leukemia) due to altered activity of transcription regulators
101
What is the consequence of a defect in N-linked glycosylation of Asn?
Congenital Disorder of Glycosylation 1 (CDG-1)
102
What is the consequence of a mutation in the DNA-binding or ligand-binding domains of the androgen receptor?
Androgen Insensitivity Syndrome
103
What is the consequence of a mutation in the microphthalmia associated transcription factor (MITF)?
Waardenburg Syndrome Type II
104
What is the consequence of a mutation in the SMN1 gene?
Exclusion of exon 7 and Spinal Muscular Atrophy
105
What is the consequence of a proline to histine mutation in MSX2?
Craniosynosis
106
What is the function of ASO oligonucleotide?
Treatment of Spinal Muscular Atrophy by promoting inclusion of exon 7
107
What is the function of DNA dependent ATPases (Ex. SWI/SNF)?
Disrupt histone octamers and DNA interactions
108
What is the function of DNA glycosylase in DNA Repair?
DNA glycosylase cleaves the N-glycosidic bond to result in an apurinic site in Base Excision Repair
109
What is the function of gyrase?
Topoisomerase in bacteria that relaxes supercoils in DNA
110
What is the function of polymerase delta?
Lagging Strand analog of DNA polymerase III
111
What is the function of polymerase epsilon?
Leading Strand analog of DNA polymerase III
112
What is the function of TFIID?
Contains TBP (TATA Binding Protein) and directs assembly of the pre-initiation complex at the promoter
113
What is the function of TFIIH?
Contains XPB helicase (opens DNA at the promoter region) and CDK7 which phosphorylates the CTD during clearance
114
What is the function of the Beta subunit (prokaryotes) and PCNA (eukaryotes)?
These act as a sliding clamp that increases the processivity of DNA polymerase III
115
What is the mode of action of alpha-amanitin?
Competitive inhibitor of RNA polymerase by binding to the bridge helix?
116
What is the mode of action of Bortezomib?
Inhibits the proteasome and decreases rates of ubiquitination
117
What is the mode of action of captopril?
Inhibits ACE (angiotensin converting enzyme)
118
What is the mode of action of HDAC inhibitors?
Inhibit protein methylation/acetylation, which are important modifications in histone modifying proteins
119
What is the mode of action of Rifampicin?
Blocks RNA exit site to inhibit transcription?
120
What is the mode of action of Tamoxifen?
Binds to the estrogen receptor, preventing binding of estrogen, which inhibits recruitment of HATs
121
What is the molecular basis of Spinal Muscular Atrophy?
Mutation of SMN1 which results in exclusion of exon 7
122
What is the poly A site consensus sequence?
AAUAAA
123
What is the role of MDM2 in regulation?
MDM2 binds to p53 and masks its activation domain and targets it for destruction; high levels of p53 activate transcription of MDM2
124
What is the role of the Shine-Dalgarno sequence?
In translation, mRNA binds the 30S subunit using this sequence
125
What is the role of Wnt signaling in Beta-catenin regulation?
Wnt signaling destabilizes the APC/Axin/GSK3 complex that targets Beta-catenin for degradation
126
What is the sliding clamp referred to as in prokaryotes? Eukaryotes?
Beta subunit; PCNA
127
What is the target of quniolones in the inhibition of DNA replication?
Quinolones inhibit topoisomerases
128
What is transcribed by RNA polymerase I?
rRNA
129
What is transcribed by RNA polymerase II?
mRNA, miRNA, siMRNA, lncRNA
130
What is transcribed by RNA polymerase III?
tRNA, specialized RNA
131
What pathology is characterized by a defect in the FMR1 gene with an increase in CGG repeats?
Fragile X Syndrome
132
What pathology is characterized by an insertion of proline into an alpha helix structure?
Thalassemia
133
What pathology is characterized by deafness and pigmentation defects of the eyes, hair, and skin?
Waardenburg Syndrome Type II
134
What pathology is characterized by developmental defects, neurological abnormality, and brittle hair?
Trichothiodystrophy
135
What pathology is characterized by feminization or undermascularization of external genitalia at birth, abnormal secondary sexual characteristic development at puberty, and infertility?
Androgen Insensitivity Syndrome
136
What pathology is characterized by multisystem disorder: growth retardation, mental retardation, craniofacial defects, and abnormally broad thumbs and big toes?
Rubinstein-Taybi Syndrome
137
What pathology is characterized by premature fusion of sutures in the skull that limits the brain’s ability to grow and craniofacial abnormalities?
Craniosynosis
138
What pathology is characterized by sun hypersensitivity, premature aging, impaired development, impaired development, and neurological degeneration?
Cockayne's Syndrome
139
What pathology is characterized by sun hypersensitivity, skin neoplasms, and neurological degeneration (later)?
Xeroderma Pigmentosum
140
What protein is involved in the balance of NEHJ and HR DSB repair?
53BP
141
What toxin comptetitively binds to RNA polymerase to prevent transcription?
alpha-amanitin
142
What types of RNA comprise the category of regulatory RNAs?
miRNA, siRNA, lncRNA
143
What types of RNA comprise the category of structural RNAs?
tRNA, snRNA, snoRNA, rRNA
144
What X-linked pathology is characterized by mental retardation, craniofacial defects, and macroorchidisim?
Fragile-X Syndrome
145
When there is a vitamin K deficiency, modification to synthesize _______ cannot occur, which results in blood thinning
gamma-carboxyglutamate
146
Which 3 trans acting factors are controlled by nuclear entry?
NF-AT, Nf-kB, and glucocorticoid receptor
147
Which DNA repair mechanism uses DNA glycosylase?
Base Excision Repair
148
Which transcription factor contains CDK7? What is the function of CDK7?
TFIIH; phosphorylates CTD during clearance
149
Which transcription factor contains TBP?
TFIID
150
Which transcription factor contains XPB helicase?
TFIIH
151
Which two trans acting factors are regulated by their intracellular concentration?
p53 and Beta catenin
