Quiz 4 Flashcards
1
Q
Purines
A
Adenine
Guanosine
Xanthine
Hypoxanthine
2
Q
Pyrimidines
A
Cytosine
Uracil
Thymine
3
Q
Uracil nucleoside and nucleotide
A
Uracil - Uridine - Uridylate
4
Q
Cytosine nucleoside and nucleotide
A
Cytosine - Cytidine - Cytidylate
5
Q
Hypoxanthine nucleoside and nucleotide
A
Hypoxanthine - Inosine - Inosinate
6
Q
Xanthine nucleoside and nucleotide
A
Xanthine - Xanthosine - Xanthylate
7
Q
PRPP Synthetase inhibitors
A
IMP, AMP, GMP, ADP,GDP
8
Q
PRPP Aminotransferase inhibitors
A
IMP, AMP, GMP, ADP, GDP, ATP, GTP
9
Q
Adenylosuccinate synthetase inhibitor
A
AMP
10
Q
IMP Dehydrogenase inhibitor
A
GMP
11
Q
Purine salvage pathways
A
Hypoxanthine/Guanine to IMP,GMP
Adenine to AMP
12
Q
Carbamoyl-P Synthetase II Inhibitor
A
UMP, UDP, UTP, CTP
13
Q
Carbamoyl-P Synthetase II Activator
A
ATP
14
Q
Aspartate Transcarbamoylase Inhibitor
A
CTP
15
Q
Aspartate Transcarbamoylase Activator
A
ATP
16
Q
Difference between CPS1 and CPS2
A
1 is in the mitochondria and for the urea cycle, 2 is in the cytosol
17
Q
Nucleoside Diphosphate Kinase specificity
A
Can be used for any of the diphosphate to produce CTP
18
Q
2 sites of ribonucleotide reductase regulation
A
Site 1: dATP binding inhibits enzyme
Site 2: binding of triphosphate triggers reduction to diphosphates
19
Q
dATP or ATP binding to site 2 is reduced to
A
UDP, GDP
20
Q
dTTP binding to site 2 is reduced to
A
GDP
reduction of UDP, CDP is inhibited
21
Q
dGTP
A
ADP
22
Q
Thymidylate synthase inhibitor
A
F-dUMP
- made from fluoruracil, fluorodeoxyuridine
23
Q
Dihydrofolate reductase inhibitor
A
Aminopterin
Amethopterin (methotrexate)
- these are folate analogs
24
Q
Why is dTMP a good target for chemo
A
It is only used for DNA
25
Allopurinol
Inhibits Xanthine Oxidase
26
What causes gout
Too much purine synthesis leading to accumulation of uric acid
- deposits in joints/kidney
- caused by foods high in nucleic acids, proteins, alcohol, diuretics
27
Lesch-Nyhan syndrome
Absence of HGPRT
- symptoms: gout, self-mutilation, intellectual disability
28
3 ways chemotherapy works on cancer
1) blocks nucleotide biosynthesis
2) kills proliferating cells
3) blocks DNA replication (nucleotide analogues)
29
Fluorouracil, Fluorodeoxyuridine
Creates F-dUMP which works as a nucleotide biosynthesis inhibitor
30
Methotrexate
Folate antagonist, kills proliferating cells
31
AraC
Arabinose analog of deoxycytosine
- blocks DNA replication with nucleotide analogues
32
Acyclovir, Gancylovir, AZT
Chain terminators
- acyclovir, gancyclovir for Herpes
- AZT for AIDS
33
5-iododeoxyuridine, araA, araC
Chain elongation inhibitors
- 5-iodo for Herpes
- araA for viral encephalitis
- araA is a more potent inhibitor of viral polymerase vs host polymerase
34
B form vs A form hydration
B from is hydrated, while A form is present in low humidity
- changes the shape of the helix
35
Z form DNA significance
GCGCGCGCGC
- spreads out genes being actively transcribed
36
Secondary DNA stabilizing factors
H bonds, vDw, ions
37
Secondary DNA destabilizing factors
electrostatic repulsion, phosphate at pH 7 (negatively charged)
38
Why does ssDNA absorb more light
Absorbs more light (260 nm) bc the bases are exposed
39
Tm
50% of DNA denatured
40
5 types of drugs included in HAART
1) Nucleoside reverse transcriptase inhibitors
2) Non-nucleoside RTI (NRTIs)
3) Protease Inhibitors
4) Entry Inhibitors
5) HIV Integrase Inhibitors
41
Non-nucleoside reverse transcriptase inhibitors (NRTIs)
Inhibit addition of nucleotides to chains using a nucleoside analog
- acyclovir, AZT
42
Negative supercoil
Underwound
43
Positive supercoil
Overwound
44
Is natural DNA negative or positive
Negatively supercoiled
45
Topoisomerase 1
break one strand, change by +1 or -1 supercoils
- requires DNA to be strained + or -
- does not affect unstrained DNA
46
Topoisomerase 2
cuts 2 strands, changes number of supercoils by 2
- can add supercoils to new DNA in prokaryotes only
47
How do topoisomerase inhibitors work
Inhibit re-ligation function by the enzyme
48
Topoisomerases 1/2 in prokaryotes and eukaryotes
Different version in each
49
Histones
small, positive proteins
50
H1 function
Linker DNA, higher-order structures
51
H2A, H2B, H3, H4 function
Nucleosome core
- DNA wrapped around is same length as Okazaki
52
Solenoid
35-40x shortening of DNA
- 6 nucleosomes per turn
53
Highly repetitive sequences
- short, tandem, AT-rich
- 10% of genome
- telomeres
- greater than 300,000 copies per genome
54
Moderately repetitive sequences
- code for highly-used genes
- SINES/LINES space out actively transcribed genes
55
Unique or single-copy sequences
- only 1% made (housekeeping genes)
- grouped in families
- pseudogenes: non-functional unique sequences
56
Myotonic Dystrophy Type 1
- more CTG repeats increases severity (onset age decrease)
- due to polymerase slipping on repeats
57
What is anticipation
increase in severity of a disease with each successive generation
58
Origin of replication
P - OriC
E - ARS
59
Protein that binds origin
P - dnaA complex
E - ORC
60
Helicase protein
P - dnaB/dnaC complex
E - MCM
61
Protein that stabilizes ssDNA
P - SSB
E - RPA
62
Protein that increases processivity
P - ß-subunit polymerase 3
E - PCNA
63
Clamp loader
P - gamma complex
E - RFC (replication factor C)
64
Protein that makes RNA primer
P - dnaG (part of primosome)
E - DNA pol ⍺
65
Protein that removes RNA primers
P - DNA Pol 1
E - RNAse H and Fen1
66
How do dnaA and ORC function?
Bind DNA binding domain and using positive histone-like proteins, causing DNA to split apart at nearby 3 AT-rich regions
67
How does priming work in prokaryotic replication
Provides an uncreated 3' OH, allowing DNA polymerase to bind
- RNA primer is 5-10 nts
68
DNA Pol I
Primer excision and DNA repair
- 3' exonuclease: proofreading, removes wrong brase
- 5' exonuclease: removes primers (nick translation)
69
Nick translation
5' exonuclease removes one base at a time until it gets to DNA
- DNA ligase then seals the open gap
70
DNA Pol III
bulk of replication, high processivity and rate
71
Core enzyme of DNA Pol III
Dimer of ⍺, ε, θ
72
ß-sliding clamp
Improves processivity, contains negative amino acids on interior to help DNA slide through
73
Function of χ subunit on 𝛾 complex
Helps transition DNA Pol III from RNA primer to making DNA
74
Replisome
Creation of a loop at at replication fork so DNA Pol III goes in the same direction on the lagging and leading strand
75
Proofreading in prokaryotes
epsilon subunit removes mismatched base with 3' to 5' exonuclease
76
Termination in prokaryotes
- ter sites: x6, 3 each side apposed 180º from OriC
- TUS protein: binds ter sites in opposite direction
- Type II topoisomerase: separates new interlinking strands, then religates
77
Protein that synthesizes DNA
P - DNA Pol III
E - DNA Pol ε, ẟ, 𝛾
78
DNA Pol 𝛾
Only in mitochondria
79
DNA Pol ε
Leading strand replication
80
DNA Pol ẟ
Lagging strand replication
- High processivity with PCNA, low without
81
DNA Pol ε
Leading strand replication
- High processivity regardless of PCNA
82
Licensing
Assembly of pre-replication complex on ARS in eukaryotes
- ORC, inactive MCM, Cdc6, Cdt1
83
Firing
Helicase activation, which activates complex to begin replication
84
hTERT
Protein component of Telomerase
- reverse transcriptase
85
hTR
Template for hTERT (RNA component)
86
t-loop
Leftover overhang that comes in and displaces ds-DNA to make D-loop-t-loop
87
Dyskeratosis Congenita
Mutations in hTERT/hTR cause premature mortality
88
Normal methylation in prokaryotes
Adenine and Cytosine
89
Normal methylation in eukaryotes
Only Cystosine
90
Methylation Heritability
1) Sites chosen during gametogenesis and embyrogenesis
2) not all C's methylated
3) maintenance methylase after replication
91
How does methylation control gene expression
Un-methylated promoter: expressed
Methylated promoter: not expressed
92
5-azacytidine
N instead of CH3 prevents methylation
- allows gene expression
93
Transition mutation
Purine-Pyrimidine to Purine-Pyrimidine
- GC -> AT
94
Transversion mutation
Purine-Pyrimidine to Pyrimidine-Purine
- AT -> TA
- can't be fixed
95
Photodimerization
Dimerization of adjacent intra-strand pyrimidines by UV
- creates Thymine dimers
96
8-oxoguanine mispaired with Adenine
Caused by ROS
97
Types of single-strand repair
1) direct base repair
2) excision repair
3) mismatch repair
98
Mechanism of direct repair of base in single-stranded repair
MGMT transfers methyl group onto itself from O6-alkylguanine
- alkylates itself and restores Guanine
99
Mechanism of NER in prokaryotes
1) UvrAB recognizes damage and bends DNA
2) UvrA leaves, UvrC joins
3) 3' cut, 5' cut, helices removes damaged piece
4) DNA Pol I replaces excised DNA, ligase seals nick
100
Mechanism of base excision repair in prokaryotes
1) Uracil-DNA n-glycosylase recognizes and removes damaged base from backbone
2) Endonuclease creates 5' nick
3) Backbone removed and replaced with new base by DNA Pol I 5' endonuclease
101
