Exam 2 Flashcards
(242 cards)
1
Q
bleomycin works on ____ as a ______
A
DNA/ strand breaker
2
Q
doxorubicin works on _______ via
A
DNA/ intercalation
3
Q
how does distamycin A interact with DNA?
A
it fits into minor grooves
4
Q
how does neocarzinostatin interact with DNA?
A
it fits into major grooves
5
Q
______ spans both major and minor grooves of DNA
A
nogalamycin
6
Q
in intercalation a covalent interaction?
A
no
7
Q
name a drug that forms a covalent complex with DNA
A
cis platin
8
Q
cis platin undergoes __ binding involving __
A
covalent/ at least one G
9
Q
the major form of binding for cis platin is
A
intrastrand - consecutive nucleotides
10
Q
name 4 ways that cis platin can bind
A
interstrand - consecutive nucleotides of opposite strands/ intrastrand - consecutive nucleotides/ intrastrand - nearby nucleotides/ either strand-G and protein
11
Q
multiple ways of binding increase
A
effectiveness as drug
12
Q
DNA is synthesized in the ______ direction
A
5’ –>3’
13
Q
_________stabilize unwound parental DNA
A
single-strand binding proteins
14
Q
In lagging strand synthesis, ____ synthesizes _____ which is ___ by ____ to form _____
A
primase/ short RNA primer/ extended/ DNA polymerase/ Okazaki fragment
15
Q
after ____ is replaced by __ by _____, ____ joins _____ to ________
A
RNA primer/ DNA/ DNA polymerase/ DNA ligase/ the Okazaki fragment/ the growing strand
16
Q
the lagging strand is synthesized _____ but the overall direction of replication is __
A
5’ to 3’/ 3’ to 5’
17
Q
__________ shortened with each round of replication
A
both ends of chromosome are
18
Q
when RNA primers are removed, gaps are filled
A
with DNA where a 3’ end is available
19
Q
____ degrade single-stranded end of template DNA
A
exonucleases
20
Q
telomeres: ends of _________, ____ chromosomes that protect and stabilize internal section of chromosome
A
linear/ eukaryotic
21
Q
telomers are ____, _____, ____ sequences of ____ nts
A
conserved/ short/ highly repeated/ 6-8 ntds
22
Q
telomers might be similar to this sequence: ______
A
5’ - TTAGGGTTA - 3’
23
Q
if a telomere is shortened too much
A
the cell stops replicating
24
Q
how long is the single strand end left after removal of terminal primer?
A
20-200 nt
25
_____ catalyzes the lengthening of telomers
telomerase
26
telomerase functions as _____ synthesizing _______from ______
reverse transcriptase/ DNA/ RNA template
27
telomerase extends the _____ end of the DNA
3'
28
do the majority of normal cells have telomerase?
no
29
reproductive stem cells have ____ levels of telomerase
moderate
30
blood, skin, and gastrointestinal cells have ___ levels of telomerase
very low
31
______% of cancer types have __ telomerase levels
90%/ high
32
telomerase level _____ from early to late stage cancer
increases
33
telomerase function is blocked by _____ that is _______
antisense DNA/ complementary to the RNA component of the enzyme
34
________ blocks telomerase function
AZT (azidothymidine)
35
_______ is a thymidine analogue whose chemical structure does not allow additional nucleotides to be added
azidothymidine
36
what is the difference between thymidine and AZT that is responsible for AZTs effects?
thymidine has a 3' OH group that allows binding to the next nucleotide. AZT has an azido (-N3) group in the S' position and cannot bind any more nucleotides
37
____ are nuclear enzymes that relax helical DNA
topoisomerases
38
topoisomerases ____ to ____. They induce ___ causing _____ and leaving ___
covalently bind/ double-stranded DNA/ induce single-stranded breaks/ DNA to unwind and relax/ single-stranded DNA available for replication
39
______ rejoins DNA ends in relaxed region and _______ from relaxed double-stranded region
telomerase/ dissociates
40
if telomerase religation were inhibited
signle-stranded breaks would accumulate leading to irreversible double stranded breaks and cell death
41
________: natural and synthetic alkaloids
camptothecins
42
synthetic camptothecins are used as
chemotherapy drugs for ovarian and colon cancer
43
the mechanism of action of camptothecins:
partially inhibit DNA topoisomerase I so that initial cleavage occurs but re-ligation is inhibited
44
cancer cells must be in the ____ phase of ______, which is the ______ for camptothecin to be effective
S/ mitosis/ DNA synthesis phase
45
camptothecin requires a prolonged exposure of tumor to drug because
not all cells are replicating their DNA at the same time
46
in transcription, ____ is transcribed from ___
RNA/ a DNA template
47
pre-mRNA is modified to mRNA in
the nucleus
48
when mRNA leave the nucleus, it goes to
the ribosome
49
mRNA is pre-mRNA minus
introns
50
amino acids are attached to ______ with the help of ___ and _____
tRNAs/ aminoacyl-tRNA synthetase/ ATP
51
mRNA translcation into protein occurs in
the cytoplasm
52
what type of bond is there between the 3' end of the tRNA and the amino acid?
an ester bond
53
what is the start codon and what does it code for?
AUG/ Met
54
what are the three stop codons?
UAA/ UAG/ UGA
55
at the start of translation, ________ binds ___ to ______. Then the ____ binds to ___. Then the ____ binds to __
mRNA initiation sequence/ mRNA/ small ribosome subunit/ methionine-tRNA/ the start codon/ large subunit of the ribosome/ the small subunit
56
When the large ribosomal subunit binds to the small, ______ fits into _____
met-tRNA/ the P site of the large subunit
57
during the elongation phase of translation, the ribosome catalyzes formation of ____ between ____ and _____.
a peptide bond/ the amino group of the incoming aa/ the carboxy terminus of the growing peptide
58
cytosolic polypeptides lack
signal sequence
59
_____ are synthesized by free ribosomes
cytosolic polypeptides
60
_____ are synthesized on rER
proteins for export
61
signal peptides bind to____ and then to ____. They are ultimately ___
signal recognition particle (SRP)/ SRP receptor protein on ER/ cleaved off new protein
62
does all translation start on free ribosomes?
yes
63
newly formed proteins with signal peptide at ____ direct ______ to ___
N-terminous/ ribosome, mRNA and protein/ ER
64
the signal peptide __. The rest of the protein __
is held in the membrane/ goes into the ER lumen
65
what happens to the signal peptide after it is cleaved by signal peptidase?
it is released to the cytoplasm and degraded
66
What happens to protein in the ER?
processing and delivery
67
rRNA and ribosomal protein components of mammalian and bacterial ribosomes subunits _____ so ___
differ/ antibiotics can preferentially target translation events and machinery of bacterial ribosomes
68
different antibiotics can block:
tRNA binding to ribosome, translocation, interaction of tRNA and mRNA codon, initiation, elongation
69
where do protein modifications occur?
rER, Golgi, eytoplasm, nucleus
70
hydroxylation on collagen proline to hydroxyproline ________
improves stability
71
phosphorylation on IF serine or threonine ____
causes disassembly
72
phosphorylation on Na+/K+ pump ________
affects ion transport
73
_______ represent a potential therapeutic target in AML
lysine acetyltransferases
74
for every one drug eventually clinically used, ___ new chemical compounds are synthesized
6-10 thousand
75
from the time a target drug is identified, it is about __ more years until it is used clinically
12
76
the total cost of making a new drug is around
1 billion dollars, half in lab research and half in clinical trials
77
for one drug successfully clinically trialed, __ have failed clinical trials
19
78
Zebra fish: _______ (____ associate) protein --> defective movement
B-amyloid/ Alzheimer's
79
Drosophila _____ associated gene --> loss of _______
Parkinson's/ dopaminergic neurons
80
Yeast: _____ protein associated with _______. Protein function unknown
SBDS/ bone marrow failure in humans
81
Is the sensitivity of human cancer cells to anticancer drugs in petri dish tests directly related to drug success in treating patient tumors?
yes
82
______ is a telomerase inhibitor that depletes cancer stem cells in breast and pancreatic cancer cell lines
Imetelstat
83
HeLa cells _______ attached to test tube, ____ active, replicated cells were split to additional tubes
cervical carcinoma cells/ mitotically
84
NR is a _____ dye
weak cationic dye
85
NR _______ by ________
penetrates cell membrane/ passive diffusion
86
NR is retaine within ________ in ______
lysosomes/ healthy cells
87
NR binds ______ in ______
anionic proteins/ lysosome
88
the amount of NR dye is ______ and replaces ____
related to cell number/ counting individual cells
89
NR dye_______ from ________
leaks/ stressed or damaged lysosome
90
decrease in total NR dye reflects ______
cell damage, death
91
NR dye can be detected by ___ or __
microscope/ extraction at end of test
92
NR dye is measured by ______ at ___
spectrometry/ 540 nm
93
_____ can give quantifiable response to drug candidate
IC50
94
the human genome contains around ___ nucleotides
3 billion
95
genes can be between _______ to ___ nucleotides
several thousand/ millions
96
functions are unknown for ___ % of genes
50
97
how many genes do humans have?
15,000 to 20,000
98
what percent of sequence is the same in all people?
99.9%
99
how many nucleotide differences are there between people?
around 3 million
100
SNPs:
single nucleotide polymorphisms - variations in sequence with no obvious negative effect, but may change drug metabolizing enzymes or ability of affected protein to interact with drug
101
iressa (______) is a _____ that is successful in treating some, not all, lung cancer
gefitinib/ kinase inhibitor
102
lung cancer cells express high levels of a mutated receptor (________) with _____
EGF-R (epidermal growth factor receptor/ over-active kinase
103
to sequence DNA, you heat strands to ___ them by _______
separate/ breaking H-bonds between base pairs
104
in DNA sequencing, after separating strands you ____ that complement __
anneal primers/ only one strand
105
a _____NTP is a chain terminating nucleotide because _____
dideoxy/ it has no 3' hydroxyl group
106
in DNA sequencing, you want ___ amounts of ddNTPs and _____ amounts of dNTPS
low/ high
107
in DNA sequencing, you use ____ (after using heat to separate double stranded DNA) to separate strands with 1 ntd size difference. Then you ______. Then ___ interprets color in gel to ____.
gel electrophorsis/ scan gel with laser to detect different fluorescent tags/ a computer program/ sequence synthesized strand
108
how many rounds of PCR does it take to yield 1 billion DNA copies?
30
109
transcription is initiated at ___
promoter region
110
_____ is an HDAC Inhibitor (SAHA) in clinical trials for advanced breast cancer
vorinostat
111
how many people in a phase I trial?
20-80
112
how many people in a phase II trial?
100-300
113
how many people in a phase III trial?
1000 - 3000
114
histones are (positively/negatively) charged (acidic/basic) proteins with about ___ aa
positively/ basic/ 120
115
histones contain numerous _____
lysines
116
lysines have a ___ charged ______ group
positively/ NH3+
117
lysine interacts with the negatively charged _____
DNA phosphate
118
there are _____ histone types. __ function as core and ___ as spacer between nucleosomes
5/ 4/ 1
119
nucleosomes: ____ and _______
4 pairs of histones at core/ ~140 bp DNA wrapped around them in <2 turns
120
nucleosomes are ___ in diameter
~10 nm
121
packing of nucleosomes depends on
histone post-translational modifications
122
chromatin fibers are about __ in diameter
20 nm
123
_______, __________, and _____ affect compaction of chromatin fibers
histone phosphorylation, methylation and acetylation
124
in histone acetylation, the ____ group on _____ is _______, reducing the interaction between histones and DNA making the chromatin
NH3+/ lysine/ covalently modified/ able to be transcribed
125
HATs:
gene expression
126
HDACs:
gene silencing
127
when chromatin structure is open, ___ has greater access to DNA
RNA pol II
128
transcription promotors may also include distant sequences further _____ where other regulatory proteins bind
upstream
129
_____ binds to TATA box
transcription factor
130
transcription factors aid RNA polymerase interaction with ____
promoter
131
__ causes release of polymerase downstream of gene
terminator sequence
132
mRNAs are processed __
in the nucleus
133
modification may _____ mRNA half-life by ___
increase/ slowing degradation
134
what is added to the 5' end of mRNA?
modified nuclotide (guanine) cap
135
what is added to the 3' end of mRNA?
poly-A tail
136
in addition to coding information, mRNA has an initiation (leader) sequence responsible for
mRNA interaction with ribosome subunit
137
the end of an mRNA is marked by the termination sequence ______
AAUAAA
138
is the poly A tail gene coded?
NO
139
introns are excised from mRNA by
spliceosomes
140
____ and _____ form scaffold for pre-mRNA excision and bonding
proteins and short RNAs
141
what kind of bonds are re-established after excision to link mRNA together?
covalent
142
what enzyme transcribes DNA into rRNA?
polymerase I
143
what enzyme transcribes DNA into mRNA?
polymerase II
144
what enzyme transcrbes DNA into tRNA?
polymerase III
145
Interphase:
metabolically active, euchromatin and heterochromatin observed, contains phases G0 - G2
146
G1:
Gap 1, hours to days or more, cell growth
147
G0:
quiescent, non-dividing cells (temporary or permanent, cease cycling)
148
S:
synthesis of DNA - telomeres replicated?
149
G2:
Gap 2 - prepare for cell division
150
M:
mitosis - nuclear and cell division
151
Prophase
chromosomes condense
152
prometaphase
nuclear membrane breaks down
153
metaphase
chromosomes align
154
anaphase
chromosomes separate
155
telophase
nuclear membrane reforms
156
cytokinesis
separation into two cells
157
when does chromosome replication occur?
during interphase
158
which cell types are permanently stopped (post-mitotic, "terminally differentiated")?
upper layers of skin, many neuronal cells, skeletal muscle, RBC
159
what cells are temporarily stopped?
liver cells, some WBC
160
what cells routinely stop and go?
some skin and gut lining cells, bone marrow cells
161
EGF is a protein that promotes skin cell replication. It is produced in many non-skin tissues. It is ______
an external positive signal
162
EGF Receptor transmits a signal ____
across a membrane
163
3 sub-regions of EGF Receptor - one projects from cell surface and __, one spans bilayer, one projects into cytoplasm and ___
binds EGF/ has kinase activity
164
The cytoplamic sub-region of the EGF Receptor attaches ______ groups to _____ in _____
-PO4/ tyrosine/ itself and other proteins
165
EGFR mutations often _____ kinase activity
hyperactivate
166
after ligand binding to EGF comes _____ formation. Then comes activation of __ and _____.. Then ____ associated with receptor are ___. These _____ then move to ___ and cause transcription of ______ (_____ and _____)
dimer/ receptor kinase/ self-phosphorylation/ cytoplasmic proteins/ phosphorylated/ nucleus/ cell cycle promoting genes/ cyclins/ cdks
167
internal positive controls cause
qualitative and quantitative changes
168
cdks =
cyclin dependent kinases
169
cyclin is a ____. Its amounts increase and decrease during the cell cycle
regulatory subunit
170
cdks are _____ that ____
catalytic subunits/ phosphorylate proteins
171
Mitosis Promoting Factors: combined activity of cyclins and Cdk promotes progression through ___ to ___
G2/ M
172
____ leads to degredation of _______
cdk/ cyclin
173
myostatin is _____
an external negative control
174
mice with low myostatin have ______ muscle mass
more
175
myostitin triggers expression of genes for __ and _____
protein degrading enzymes/ encoding cell cycle "brake" proteins
176
Myostatin binding leads to receptor ___. Then __ proteins with ______ are recruited and _____ ensues. ____ cytoplasmic proteins move to ______ where they bind ______ and _____ ( ___ and ______)
dimerization/ transmembrane/ kinase domains/ phosphorylation cascade/ phosphorylated/ nucleus/ specific DNA sequences/ increase transcription of select genes (p21/ p53)
177
___ and ____ bind and inactivate cyclins, blocking entry in to ____ phase. They are frequently mutated in cancers
p27/ p21/ S
178
____ blocks cell cycle if DNA is damaged. It also slows ____ - overall DNA replication is slowed.
p53/ topoisomerase
179
by slowing replication, p53 allows for more time for correcting mutated DNA bases by "proofreading", a function of ______
DNA polumerase
180
HPV protein degrades _____ protein in infected cell
p53
181
to pass the G1 checkpoint you need ___, __ and ____
adequate cell size, nutrients available, growth factors present
182
to pass the G2 checkpoint you need ____ and ___
adequate cell size/ chromosome replication is complete
183
to pass the metaphase checkpoint you need ____
all chromosomes to be attached to functional mitotic spindle
184
________ proteins are activated by mutagens such as __, ____, and _______
checkpoint/ UV light/ radiation/ free radicals
185
apoptosis: death from ____ process, started by ___ signal
internal/ external
186
in apoptosis, ___ enzymes are activated
caspase
187
in apoptosis, the membrane is shed as intact _____
"blebs"
188
in apoptosis, the membrane is altered which can trigger ________ by ____
phagocytosis/ macrophages
189
in apoptosis, ________ collapses
nuclear and cytoplasmic cytoskeleton
190
in apoptosis, _____ is digested
nuclear DNA
191
caspases =
Cysteine Aspartic acid-Specific ProteASES
192
caspases ______ after recognizing a 4 amino acid repeat in the substrate protein
cleave protein
193
caspases are normally present in healthy cells as inactive precursor enzymes (___) with little or no protease activity
zymogens
194
____ caspases are able to auto activate and _____ of other caspases
initiator/ initiate proteolytic processing
195
effector caspases are activated by
upstream initiator caspases
196
effector caspases _______ during apoptosis
cleave the majority of substrates
197
Extrinsic pathway apoptosis:
receptor-mediated
198
extrinsic pathway: peptide binds receptor (may be secreted from neighboring damaged cells) causing a receptor shape change that causes ______
initiator caspase auto-activation
199
the extrinsic pathway leads to ______ (____) activation with digestion of downstream caspases and other proteins
caspase 8/ initiator
200
cleavage of BID to truncated tBID --> tBID has similar effect as __ --> disrupts mitochondrial membrane integrity. Insertion triggers apoptotic signal in ___
Bax/ mitochondria
201
intrinsic: __ pathway
mitochondria
202
intrinsic pathway: apoptotic signals (including certain chemo drugs) cause __ and or _____ insertion into the mitochondria membrane, disrupting it and releasing ____ and ___ from mitochondria
Bax/ tBID/ several proteins/ Ca++
203
____ is an auto-initiator
caspase 9 (also caspase 9)
204
After initiator caspases:
1. effector caspases ______
2. DNAases move to ______ where they __
3. effector capsases move to ___ and ___
4. effectors digest _____
5. effectors digest ____
6. effectors digest _____
1. digest inhibitors of DNAase (ICAD)
2. nucleus/ digest DNA between nucleosomes
3. nucleus/ digest lamins
4. microfilaments
5. adhesion plaque proteins
6. translation factors
205
______ is a synthetic analogue of cortisol used as an anti-inflammatory. It induces specialization of adult blood somatic cells to mature progeny (non-replicating cells)
dexamethasone
206
_____ stimulates adult blood somatic stem cell replication from donor in lab prior to transplant
PGE2
207
unipotent example
replicating adult skin cells
208
multipotent example
bone marrow
209
pluripotent:
can produce cells of any tissue or body layer, example, blastocyst ICM (inner cell mass) cells
210
totipotent:
generates all cells and tissue types of an embryo
211
endoderm:
lungs, GI tract, bladder
212
mesoderm:
bone marrow, muscle, bone
213
ectoderm:
skin, eyes, brain
214
CLP (______) progeny:
committed lymphoid precursor: T-cells, B-cells
215
CMP (______) progeny:
committed myeloid precursor: RBCs, megakaryocytes, basophils
216
Intestinal Stem Cells divide to produce
1 ISC and 1 transient amplifying (TA) cell
217
TA cells go through limited cell cycles. Their progeny differentiate into _____ and __
goblet cells/ enterocytes
218
how often is the small intestine lining renewed?
every 5 days
219
skeletal muscle stem cells adopt a _______ and retain _______
dormant cell state post mortem/ retain regenerative capacity
220
_______ contributes to long term viability
cell quiescence (G0)
221
for iPS cells, ____ are inserted into adult cell genome using ____
4 different genes/ viruses
222
in making iPS cells, the protein products of reprograming genes cause loss of _____ and gain of _____
adult cell-specific function/ ES cell traits
223
___ 1st stage of cancer, caused by ____
initiation/ initiators
224
examples of initiators:
UV light, some hydrocarbons, cigarette smoke
225
______ 2nd stage of cancer, caused by ____
promotion/ promoters
226
Is the promotion stage directly mutagenic?
no
227
examples of promoters:
some environmental toxins, HPV protein that inactivates p53 function
228
_____ - epithelial cells (~90% of all cancers)
carcinoma
229
______ - connective tissue or muscle cells
sarcoma
230
______ - hematopoietic (blood) cells
leukemia
231
______ cause multiple single ntd changes
chemical carcinogens
232
________ causes chromosome breaks
ionizing radiation
233
___ DNA integration disrupts cell's genes
viruses
234
colon cancer studies: progressive accumulation of mutations ___
confers additional growth advantage
235
most cancers originate from a single cell --> _______ of this cell
clonal expansion
236
CSC have a long ___ phase and ______
G1 phase/ don't replicate often
237
CSC daughter cells have shorter __ phases and _____ but ____
G1/ replicate frequently/ are likely to cease after several rounds of cell cycle
238
CSCs have high levels of ___, _____, and ___
telomerase/ EGFRs/ anti-apoptotic proteins like Bcl2
239
there are very high levels of _____ on breast CSC membranes
HER2 receptors
240
____ dimerizes with _____ to activate cell replication
HER2/ EGFR
241
______ bocks HER2 receptor function. It is a lab-made antibody against HER2 extracellular domain
trastuzumab
242
antibody binding stimulates ____ and reduces ___
patient immune system to attack tumor cell/ EGF-R1::HER2 ability to transdyce growth-promoting signal across cell membrane
