FMS Week 1 Flashcards
1
Q
Ataxia telangiectasia
A
Results from mutations in ATM gene, spider veins, loss of motor control, immunodeficiency, sensitivity to radiation
2
Q
Neurofibromatosis
A
Inherited cancer syndrome caused by mutation in NF1 gene
3
Q
DNA polymerase δ
A
Leading and lagging strand synthesis and base excision repair
4
Q
XPC
A
NER gene, xeroderma pigmentosum assoc.
5
Q
GEF
A
A GTP meditator for G-proteins
6
Q
What is the second step of RNA modification?
A
The RNA is cleaved at the polyA signal, the tail is synthesized by polyA polymerase, PABPN1 (poly A binding protein 1) stops synthesis at 200-300bp
7
Q
what are the similarities of the 2 apoptosis pathways?
A
they both activate the same effector caspases
8
Q
mutation in mismatch repair gene (MMR)
A
Lynch syndrome, most commonly results in hereditary non-polyposis colon cancer (HNPCC)
9
Q
2 types of anchoring junctions
A
adherens junctions and desmosomes
10
Q
aflatoxins
A
carcinogens from peanut/grain mold
11
Q
what is the biggest difference between dephosphorylation and GTP hydrolysis?
A
GTP hydrolysis is not mediated by an enzyme
12
Q
Bloom syndrome
A
results from mutation in BLM gene of homologous recombination, short stature, narrow face with prominent nose, skin-sun sensitivity, facial rash, immunodeficiency, cancer, possible mental retardation
13
Q
translation initiation
A
40s subunit joins mRNA at 5’ region, scans for the first start codon in the proper context, 60s subunit joins and translation begins
14
Q
carcinogens from charred meat
A
heterocyclic amines
15
Q
aneuploidy
A
less or more than an exact multiple of the haploid set of chromosomes
16
Q
erythromycin
A
binds to the 50s subunit and inhibits translocation (prokaryotes)
17
Q
what type of molecules are second messengers?
A
small molecules that aplify the signal of the first messenger (ligand)
18
Q
1000-fold increase of skin cancers, “children of the night”
A
Xeroderma pigmentosum
19
Q
where does DNA methylation occur?
A
C-G adjacent basepairs
20
Q
JAK-STAT Pathway
A
cytokines bind receptor, JAKs phosphorylate each other, JAK binds and activates STAT through phosphorylation, STAT (complex) is a transcription factor
21
Q
cycloheximide
A
inhibits translocation (blocks translational elongation)(eukaryotes)
22
Q
What is PTEN?
A
PTEN inhibits PIP2 to PIP3 secondary messaging, indirectly leading to promotion of apoptosis (AKT indirectly leads to degradation of p53) and inhibition of cell growth
23
Q
Werner Syndrome
A
results from mutations in WRN gene of homologous recombination and DNA replication, short stature, premature aging, cancer
24
Q
CNV
A
copy number variants
25
CDKN2 family
bind and inhibit only D-CDK4/6 (restriction point)
26
What effect do Xrays have on DNA?
strand breakage
27
tight junction
seals gaps between epithelial cells
28
what is myc?
a transcription factor for cyclin D
29
receptor of RAS-MAPK
tyrosine kinase
30
ATM gene
gene associated with homologous recombination in double-stranded breakage
31
how do hydrophillic signals act?
surface receptors trigger signal transduction through to effector proteins that can act both inside and outside the nucleus
32
what facilitates phosphorylation?
ATP (to ADP) and a protein kinase
33
XPA
NER gene, xeroderma pigmentosum assoc.
34
DNA mismatch repair
Guided by mismatch proofreading proteins cut out segment of strand with "nick" so that DNA pol can resynthesize
35
prophase
chromosomes condense, mitotic spindle forms, nucleus disassembles, chromosomes begin attaching to mitotic spindle
36
metaphase
chromosomes line up
37
cytokine
small proteins that stimulate differentiation/proliferation of immune cells
38
Bad
apoptotic sensor
39
FANC
interstrand DNA crosslink repair gene, assoc. w/ fanconi anemia
40
pemphigus vulgaris
blistering disease caused by autoantibodies to desmosomal proteins
41
DNA polymerase ε
Leading strand synthesis and base excision repair
42
7-TM receptor
large serpentine domain that is usually coupled to large G-protein
43
membrane-mediated signalling
signals communicate through the membranes of adjacent cells
44
what family is p16?
CDKN2
45
2 ways splicing can regulate translation
alternative introns/exons, differential splice sites within an intron
46
cyclin-CDK G2/M transition (entry to mitosis)
A-CDK1
47
what is the biggest difference between dephosphorylation and GTP hydrolysis?
GTP hydrolysis is not mediated by an enzyme
48
carcinogens from peanut/grain mold
aflatoxins
49
Ras
small G-protein, activated (GTP) through tyrosine-kinase complexes
50
what are the 2 pathways of apoptosis?
Intrinsic (mitochondrial) and extrinsic (death receptor)
51
what is a procaspase?
an inactive caspases that cleave eachother to activate, then cleave executioner caspases to activate them in a cascade
52
snRNPs
guide splicing process, make up the splicosome
53
Xeroderma Pigmentosum
high risk of all skin cancers, results from mutation in any XP gene (NER gene): XPA, XPC, ERCC2, ERCC4, ERCC5
54
actin-linked cell matrix junction
actin anchors to extracellular matrix (basal lamina). basal "adherens"
55
What are the pro-apoptotic sensors and what do they do?
Bad, Bim, Bid, Puma, and Noxa. They are BH-3 only proteins. They sense cellular stress/damage and take out the anti-apoptotic regulators to start apoptosis.
56
receptor of PI3K-AKT pathway?
receptor dimers with intrinsic kinase domains or that bind intracellular kinases
57
direct ligation
DNA-protein kinase and Ku allign dsDNA breaks, usually results in bp deletions
58
Restriction point pathway
Growth factors trigger signalling pathway that upregulates myc (cyclin D transcription factor), cycD activates CDK4/6, D-CDK4/6 phosphorylates Rb, inactivated Rb (hyperphosphorylated) no longer inactivates E2F, freed and activated E2F is transcription factor for S phase genes such as cyclin A
59
WRN
gene involved in homologous recombination and DNA replication, codes for a DNA helicase
60
Bcl-XL
anti-apoptotic regulator
61
BRCA1/2
gene associated with homologous recombination in double-stranded breakage
62
non-homologous end joining
resects ends to uncover 2-3 nucleotide micro-homology
63
fragile-X syndrome
caused by nucleotide expansion mutations
64
RAS-MAPK pathway
growth factors bind receptor, Ras is activated by GTP exchange factor (GEF), Ras activates (p) Raf, Raf activates (p) Mek, Mek activates (p) Erk (MAPK). Erk phosphorylates target proteins including transcription factors such as Myc
65
membrane-mediated signalling
signals communicate through the membranes of adjacent cells
66
ERCC2
NER gene, xeroderma pigmentosum assoc.
67
GPCRs
large G-proteins
68
how to hydrophobic signals act?
the enter the plasma membrane and bind with receptors in the cytoplasm, then move into the nucleus
69
myotonic dystrophy
caused by nucleotide expansion mutations
70
euchromatin
more relaxed chromatin, more transcriptionally active
71
what is p53?
a tumor supressor gene that is involved in the restriction point pathway, DNA damage checkpoint pathway, and the apoptosis pathway
72
cAMP-PKA pathway
Peptide hormone is ligand for 7TM receptor, which activates adenylate cyclase, which activates (p) cAMP, which removes inhibitor on protein kinase A (PKA), PKA enters the nucleus and activates transcription factors
73
receptor of JAK-STAT
cytokine receptor coupled to JAK
74
steroid receptors
gene-specific transcription factors that are activated by hormone binding
75
how does methylation deactivate genes?
attracts histone deacytylases (HDAC), compacts histones around promoters
76
mitotic/spindle assembly checkpoint
Mad2 recruited to kinetochore, Mad2 inhibits APC/C (an ubiquitin ligase), mitotic proteins and cyclins (A&B) cannot be degraded by 26S, and the cell cycle is arrested in mitosis until securin can restore loose chromatids
77
steroid receptors
gene-specific transcription factors that are activated by hormone binding
78
cytokine
small proteins that stimulate differentiation/proliferation of immune cells
79
HNPCC
"Lynch syndrome", colorectal cancer, MMR mutation: MSH2/3/6, MLH1, PMS1/2
80
NF1
a gene that accumulates regulates Ras when growth factor is not present to initiate it
81
desmosomes
connects intermediate filaments between cells
82
what activates apoptosis?
caspases (cysteine proteases that cleave proteins after aspartic residues)
83
CDKN1 family
CKI family that inhibits multiple cyclin-CDK complexes, broad spectrum
84
streptomycin (aminoglycosides)
inhibit initation and cause misreading of mRNA (prokaryotes)
85
Beta-thalassemias
mutation in Beta-globin subunit of hemoglobin caused by mutation in promoter, often the result of splice-site mutations
86
what facilitates dephosphorylation?
protein phosphatase
87
chemokine
agent that attracts motile cells through receptor mediated signalling
88
first messenger of cAMP-PKA pathway
peptide hormones (epinephrine etc.)
89
Proofreading
3' to 5' exonuclease activity of DNA pol
90
Neurofibromatosis
Inherited cancer syndrome caused by mutation in NF1 gene
91
Telomerase
synthesizes incomplete 5' ends of the lagging strands, levels are mostly high in rapidly dividing cells (embryos and cancer)
92
CKIs
cyclin-dependent kinase inhibitors, sterically inhibit
93
IP3-PKC pathway
Receptor activates large G protein, which activates phospholipase C, which cleaves PI4,5P2 to IP3 and DAG. IP3 binds to SER Ca channels to release Ca. Ca binds to PKC which has bound to DAG, activating the complex, PKC complex phosphorylates many substrates including nuclear transcription and cytoplasmic regulatory proteins
94
Describe a SINE
Short interspersed nuclear elements, non-coding DNA, use rev transcriptase from LINES, most common are ALU repeats
95
RISC
RNA-induced silencing complex, pairs miRNAs with compliments on mRNA for possible translational repression and rapid/eventual degredation
96
PI3K-AKT pathway
ligand binds receptor, facilitates phosphorylation of PIP2 to PIP3, PIP3 stimulates PDK1, which activates AKT(PKB) through phosphorylation, AKT(PKB) is a master regulator for cell growth and against programmed cell death
97
what is p53s role in the restriction point?
p53 is a growth inhibitor that upregulates p16 and inhibits the restriction point pathway, leaving Rb in a hypophosphorylated state (bonded to E2F)
98
iPSC
induced pluripotent stem cells
99
MCL1
anti-apoptotic regulator
100
differences between apoptosis and necrosis
necrosis is pathological rather than physiological, membranes break up, contents may leak out and cause inflammation.
Apoptosis is physiological [programmed cell death, cell shrinks intact, contents may be released in apoptotic bodies
101
What does the Bcl-2 family do?
They control mitochondrial outer membrane permeability (MOMP)
102
paracrine signalling
signaling molecules that act on nearby cells
103
Which type of nucleotide is more at risk to DNA damage due to metabolism?
purines
104
chemokine
agent that attracts motile cells through receptor mediated signalling
105
heterochromatic
more condensed, repressed chromatin
106
First messenger of RAS-MAPK
growth factors
107
Large Heterotrimeric G-Protein Function
Ligand stimulates alpha subunit, which can then leave rest of complex to activate an effector molecule, hydrolyzing GTP so the subunit can return to the complex
108
MLH1
MMR gene
109
adherens junctions
connects actin filaments between cells
110
Bim
apoptotic sensor
111
chloramphenicol
inhibits the peptidyl transferase activity of the 50s ribosomal subunit (prokaryotes)
112
PCNA
proliferating cell nuclear antigen, "sliding clamp", inhibited by p21 so that DNA pol cannot stay attached
113
GAP
A GTPase activating protein, indirectly results in GTP hydrolysis
114
how does acetylation activate genes?
recruits histone actelation transferase (HAT) to move histones and open gene
115
what facilitates dephosphorylation?
protein phosphatase
116
cyclin-CDK at restriction point
D-CDK4/6
117
Ras
small G-protein, activated (GTP) through tyrosine-kinase complexes, growth factor initiated protein that is often an oncogene when unregulated
118
Base Excision Repair
resects and replaces small lesions (modified bases)
119
translesion DNA replication
NER
120
What are the pro-apoptotic effectors and what do they do?
Bax and Bak. They contain BH domains 1-3. They oligomerize to form pores in the outer mitochondrial membrane making it permeable.
121
puromycin
causes premature chain termination by acting as an analog of aminoacyl-tRNA (prokaryotes and eukaryotes)
122
ERCC5
NER gene, xeroderma pigmentosum assoc.
123
difference between BER and NER
NER is for helix distorting adducts and requires removal of large fragment
124
mitogen
a growth factor that stimulates proliferation
125
spider veins, sensitivity to radiation, loss of motor control
ataxia telangiectasia
126
What is ErbB-2?
A RAS-MAPK type growth factor receptor that can be blocked in certain breast cancers
127
what family is p21?
CDKN1
128
gap junction
"pipeline" allows passage of small water-soluble molecules between cells
129
integrins
allow proteins on outside of cell to sense state of extracellular matrix, connected to actin cytoskeleton
130
Bax
pro-apoptotic effector
131
what is the second messenger in cAMP-PKA pathway?
cAMP
132
cyclin-CDK in S phase (during DNA replication)
A-CDK2
133
Interstrand crosslink repair
repairs big helix distorting lesions, single nucleotide
134
sequence of splicing
Branching nucleotide -OH attacks 5' splice site, then 3'-OH of removed intron attacks 3' splice site leaving exons attached and introns in loop structure
135
Describe a LINE
Long interspersed nuclear elements, non-LTR, non-viral, retrotransposon, Only line-1 can transpose
136
purpose of JAK-STAT Pathway
stimulates blood cell growth and proliferation
137
receptor of IP3-PKC pathway
7TM serpentine
138
first messenger of JAK-STAT
cytokines (blood cell proliferation factors)
139
purpose of PI3K-AKT pathway?
controls cell growth and apoptosis pathways (AKT does through negative control of p53 via MDM2 mediation)
140
mitogen
a growth factor that stimulates proliferation
141
cyclin-CDK G1/S transition (beginning of DNA replication)
E-CDK2
142
PMS2
MMR gene
143
MSH2/6
MMR gene
144
largest class of genes
transcription factors
145
anaphase
separation of sister chromatids
146
what protein controls the restriction point?
Rb (retinoblastoma protein)
147
first messenger of IP3-PKC pathway
selected growth factors, mitogens, immune signals (histamine)
148
DNA polymerase α
DNA replication and primer synthesis
149
DNA damage checkpoint pathway
cyclin-CDKs activate ATM/ATR, ATM/ATR phosporylate and activate Chk1/Chk2, Chks phosphorylate/inhibit substrates like Cdc25 and p53, Cdc25 can no longer dephosphorylate CDKs leaving them inhibited. P53 upregulates p21
150
Which type of nucleotide is more at risk to exogenous DNA damage?
pyrimidines
151
actinomycin D
binds to DNA and blocks RNA Polymerase elongation
152
what facilitates phosphorylation?
ATP (to ADP) and a protein kinase
153
Noxa
apoptotic sensor
154
Bid
apoptotic sensor
155
What are the first steps of RNA modification?
The 7-MeG cap created by enzymes at the CTD (nose) of RNA Pol II and is added just after RNA Pol II leaves the promoter
156
What disease is caused by mutation in the NF1 gene?
Neurofibromatosis
157
DNA methyltransferases
copy methylation patterns in newly replicated DNA in mitosis, "cellular inheritance"
158
what is the execution phase of apoptosis?
executioner or effector caspases degrade cellular components
159
Friedreich ataxia
caused by nucleotide expansion mutations
160
purpose of cAMP-PKA pathway
stimulates transcription of specific genes including regulators of metabolic pathways
161
Nucleotide Excision Repair
Repairs big helix distorting lesions, single nucleotide
162
first messenger of PI3K-AKT pathway?
selected hormones (eg Insulin), growth factors and cell survival ligands
163
Fanconi anemia
results from mutations in FANC genes of interstrand DNA crosslink repair, short stature, developmental abnormalities, bone marrow disorders, cancer
164
Bak
pro-apoptotic effector
165
alpha-Amanitin
toxin from poisonous mushroom Amanita phalloides, inhibitor of RNA pol II
166
What disease is caused by mutation in the NF1 gene?
Neurofibromatosis
167
elements of the core promoter?
TATA box, initiation site (INR), downstream promoting elements (DPE)
168
What is mTOR?
mTOR is activated by AKT. mTOR activates translation by activation the ribosome and inhibiting a translation initiation inhibitor
169
purpose of IP3-PKC pathway
activation of calcium stores and PKC, which plays roles in membrane structure change, transcriptional regulation, immune response, and cell growth
170
what is the apoptotic pathway in most mammalian cells?
intrinsic
171
What are the phases of apoptosis?
initiation phase and execution phase
172
GEF
GTP exchange factor
173
how much of the nuclear genome codes for proteins?
1.5%
174
endocrine signalling
signalling to elsewhere through the circulatory system
175
Puma
apoptotic sensor
176
receptor of cAMP-PKA pathway
7-TM serpentine
177
telophase
mitotic spindle breaks down, two nuclei form, chromosomes decondense, organelles reassemble
178
what disease is caused by autoantibodies to desmosomal proteins?
pemphigus vulgaris
179
tetracycline
binds to the 30s subunit and inhibits binding fo aminoacyl-tRNAs (prokaryotes)
180
Single stranded breaks
PARP (polyADPribose polymerase) senses break and recruits BER enzymes to repair
181
Myc, Max, & Mad
Dimer transcription factors, MycMax acts as activator, MadMax acts as repressor
182
acute myeloid cancers, short stature, developmental abnormalities, bone marrow disorders
fanconi anemia
183
cytokinesis
division of cytoplasm to form 2 new cells (starts in late anaphase and finishes shortly after telophase)
184
ERCC4
NER gene, xeroderma pigmentosum assoc.
185
most important difference about meiosis
crossover during prophase I
186
Bcl-2
anti-apoptotic regulator
187
Homologous recombination
Uses homologous sequence as template to repair double stranded breaks and interstrand crosslinks, "staggered"
188
SNP
single nucleotide polymorphism, across genome, 2 variants across population
189
What are the anti-apoptotic regulators and what do they do?
Bcl-2, Bcl-XL, and MCL1. They contain BH domains 1-4. They keep the outer mitochondrial membrane impermeable.
190
Huntington's disease
caused by nucleotide expansion mutations, autosomal dominant
191
Polycyclic aromatic hydrocarbons
mutagen/carcinogen chemicals from smoke and fossil fuels
192
how much of the genome codes for introns?
26%
193
what is initiation phase of apoptosis?
initiator caspases become active
194
hemidesmosome
anchors intermediate filaments to extracellular matrix (basal lamina). basal "desmosome"
195
cyclin-CDK in mitosis
B-CDK1
196
endocrine signalling
signalling to elsewhere through the circulatory system
197
short stature, premature aging, cancer
Werner Syndrome
198
short stature, narrow face w/ prominent nose, sun-skin sensitivity, butterfly-shaped facial rahs, immunodeficiency, cancer
Bloom syndrome
