Week 2 Flashcards
1
Q
Silent mutation
A
No change in amino acid
2
Q
Missense mutation
A
Changes amino acid in protein w/ either no effect on protein function or completely changes function
3
Q
Nonsense mutation
A
Codon changed to stop codon
4
Q
Frame shift mutation
A
One ore more nucleotide deleted or inserted into ORF
out of frame causes change in amino acid sequence
5
Q
Wobble hypothesis
A
Explains why so many alternative codons for amino acid differs by third nucleotide
Refers to tRNA binding to mRNA sequence
6
Q
Aminoacyl tRNA
A
Catalyzes activation of aa by transferring AMP to COOH end
Then transfers aa from aa-AMP to cognate tRNA
7
Q
Translation of mRNA steps
A
tRNA BINDING
peptide bond formation
Large subunit translocation
Small subunit translocation
8
Q
Elongation factors for translation
A
Binds GTP and aminoacyl tRNA and escorts to ribosome (checks is amino acid -tRNA match is correct
Critical proofreading steps in protein synthesis
9
Q
Ribosomal complex sites
A
Acceptor (A) site
Peptidyl (P) site
Empty (E) site
10
Q
Stop codons
A
UAA, UAG, UGA
U R ANNOYING, U GO AWAY, U R GONE
11
Q
Streptomycin
A
Binds 30s to disrupt translation
12
Q
Shiga toxin
A
Binds 60s subunit and disrupts elongation
13
Q
Clindamycin and erythromycin
A
Bind 50s subunit to disrupt translocation of ribosome
14
Q
Tetracycline
A
Bind 30s subunit to disrupt elongation
15
Q
Polysomes
A
Clusters of ribosomes that attach to single polypeptide chain making protein synthesis more efficient
16
Q
Protein sorting sequence for mitochondria
A
N terminal hyrophobic a-helix
17
Q
Protein sorting sequence for nucleus
A
Lys and Arg rich terminal domain
18
Q
Protein sorting ER signal sequence
A
Positively charged amino acids at N-terminus
19
Q
ER retaining signal sequence
A
Lys, Asp, Glu, Leu
20
Q
Protein sequence destined for PM
A
Apolar N terminus
21
Q
HSP 70
A
Protects unfolded proteins as they pass through TOM and TIM
22
Q
Chromosome morphology
A
Metacentric
Submetacentric
Acrocentric
Telocentric
23
Q
Chromosome areas
A
P arm
q arm
Centrosome
24
Q
Proband in a pedigree
A
First diagnosed person in pedigree
25
Protein sorting sequence for mitochondria
N terminal hyrophobic a-helix
26
Protein sorting sequence for nucleus
Lys and Arg rich terminal domain
27
Protein sorting ER signal sequence
Positively charged amino acids at N-terminus
28
ER retaining signal sequence
Lys, Asp, Glu, Leu
29
Protein sequence destined for PM
Apolar N terminus
30
HSP 70
Protects unfolded proteins as they pass through TOM and TIM
31
Chromosome morphology
Metacentric
Submetacentric
Acrocentric
Telocentric
32
Chromosome areas
P arm
q arm
Centrosome
33
Proband in a pedigree
First diagnosed person in pedigree
34
Autosomal dominant inheritance
Only one allele is needed for expression
Recurrent risk for having affected children is 50%
Ex. Postaxial polydactyly
35
Autosomal recessive
Both alleles needed to influence phenotype
| Ex. Tyrosine-negative albinism
36
X linked recessive inheritance
Ex. Duchenne muscular dystrophy
37
X linked dominant
Very rare, no carriers
| Males transmit to only females
38
penetrance
Frequency a gene manifests itself
| 100% of individuals inheriting genetic defect show clinical presentation (phenotype) = 100% penetrance
39
Variable expressivity
Describes the range of phenotype that vary between individuals with specific genotype
40
Locus heterogeneity
Single disorder caused by mutations in genes at different chromosomal loci
Ex. Osteogenesis imperfecta, mutation in collagen genes at either chr 7 or 17, either mutation exhibits the same phenotype
41
Nondisjunction
Homologs fail to separate
42
Aneuploid
Cell with abnormal number of chromosomes
43
Euploidy
Cells with normal number of chromosomes
44
G1 checkpoint
Correct DNA damage before continuing
45
G2 checkpoint
Verify completeness of genomic duplication
46
Metaphase checkpoint
Ensures chromosome are attached to mitotic spindle
47
Nucleoside analogue inhibitors of DNA synthesis
analogues lack 3' hydroxyl group
| inhibits DNA polymerase
48
Xeroderma pigmentosum
skin is extremely sensitive to sunlight
causes thymine dimers to form
XP patients lack complete nucleotide excision repair (NER) complex
49
hereditary nonpolyposis colorectal cancers
involves mutation in mismatch excision repair (MER) complex
| increased susceptibility to nonpolyposis colon cancers
50
Fragile X mental retardation
expanded CGG repeats in the FMR1 gene
leads to increased methylation and silencing of genes
as methylated repeats reach promoter, transcription is turned off
51
histone acetylation and methylation
losens DNA interaction with histone
| aids in replication
52
nucleosome
basic unit of chromosome packing
| DNA wound around Histone
53
Size of human genome
26,000 genes
54
Copy number variations
differences in genome
| basis for our differences and for disease states
55
DNA helicase
unwinds DNA and hydrolyzes ATP
56
single-stranded DNA binding proteins
bind to exposed SS DNA during replication
| prevents hairpins
57
DNA primer
directs directionality
58
DNA primase
synthesizes RNA primer 7-10 ribonucleotides long
then DNA polymerase extends with dNTPs
begins the synthesis of new DNA chains
59
topoisomerase
```
relieves supercoiling (called DNA gyrase in bacteria)
breaks phosphodiester bond
```
60
DNA ligase
seals nicks in dna strand
61
spontaneous DNA damage
depurination and deamination
| leads to deletions or base pair substitutions in daughter strand during replication
62
UV radiation DNA damage
forms pyrimidine dimers
63
problem with methylated cytosines
produces T paired with G
| special DNA glycosylase removes the T
64
Direct enzymatic repair
DNA photolyase
| catalyzes breakage of linked pyrimidines
65
Base excision repair
DNA glycosylases + endonucleases
fixes single base mismatches
flip out DNA to detect damage
66
Mismatch excision repair
removes the mismatch causing the deformation
MER complex
Hereditary nonpolyposis colorectal cancers caused by defect in MER complex
67
Recombination repair
occurs after double strand breaks or inter strand cross linking
Non homologous end joining
Homologous recombination
- genetic info form undamaged strand is used to fix the the damaged strand
68
Transcription coupled repair
type of NER
initiated when RNA polymerase stalls at lesion
RNA polymerase recruited repair proteins
Defects in TCR lead to Cockayne syndrome
69
translesion synthesis
Uses DNA polymerase isozymes that do not have proofreading capabilities
70
Cockayne syndrome
defect in transcription coupled repair
| characterized by developmental and neurologic delay, photosensitivity and premature aging
71
BRCA mutations and breast cancer
BRCA1 and BRCA2 are tumor suppressor genes
| Mutations lead to increased risk duh
72
siRNA
regulate gene expression by degrading select mRNA
73
miRNA
block translation of selective mRNA
74
snRNA
packages as part of splicosome
| involved in splicing and export of mRNA
75
RNA polymerase I
involved in synthesis of rRNA
76
RNA polymerase II
synthesizes mRNA, snRNA and miRNA
77
RNA polymeraseIII
synthesizes tRNA
78
coding strand
non-template strand
79
transcription start site
+1 position of gene
has A or G
site where transcription factors and RNA polymerase bind
80
transcription stop site
poly A tail
81
promoter
upstream sequence where transcription factors bind and recruit RNA polymerase
82
enhancers/silencers
binding sites for transcription factors
| influence rate of transcription
83
general transcription factors
aids RNA polymerase binding to promoter to initiate transcription
TFIIA, TFIIB, TFIIC, TFIID
84
initiation of trancription
begins with binding of TFIID to TATA box
| subunit of TFIID is TBP that binds TATA box
85
Histone acetyl transferase (HAT)
adds acetyl group to histone
| loosens interaction with DNA
86
Histone deacetylases (HDACs)
removes acetyl group from histone
87
Chr 16p11.2
Chromosome 16
Region 1
Band 1
Sub-Band 2 on p arm
88
independent assortment
daughter cell receives any combination of maternal and paternal homologues during meiosis
89
genetic recombination
crossing over during prophase1 of meiosis
90
Prader Willi syndrome
Methylation of one copy of chr 15 and deletion of the paternal copy of chr 15
Leads to uncontrolled eating and obesity
91
Angelman syndrome
imprinting of paternal chr 15 and deletion of mothers chr 15
| neurodevelopment disorders
92
consanguinity
mating with your cousin
estimated that we have 1-5 recessive mutation lethal to offspring if matched with another carrier
Mating with first cousin increases risk up 9%
dont mate with your cousin
93
polygenic
variations in traits caused by multiple genes
94
liability distribution
for diseases that don't follow the bell-curve for multifactorial diseases
95
multifactoral diseises
caused by simultaneous influence of multiple genetic and environmental factors
96
Permanent cell type
Remains in G0 phase
cannot be regenerated
neurons, cardiomyocytes, RBCs
97
Stable (quiescent) cell type
have ability to exit G0 to G1
| Hepatocytes, epithelial cells
98
Labile cell type
never enter G0
constant divisions
gut epithelium, skin, hair follicle, bone marrow
99
ubiquitin ligase
targets cyclin/CDKs for proteolysis by polyubiquitination
| Can also target CKIs
100
retinoblastoma
mutation in both RB genes
Hereditary and non-hereditary forms
Two hit hypothesis
Tumor suppressor gene
101
p53 and cancer
tumor suppressor gene
two hit hypothesis
includes Li-Fraumeni syndrome and ataxia telangiectasia
102
Replicative cell senescence
somatic cell division ceased
Due to shortening of telomeres
Somatic cells don't have telomerase to preserve telomere length
103
RAS and Cancer
Ras is oncogene
| Mutation locks Ras in active state = increased signaling
104
neurofibromatosis
- Growth of tumor from nerve tissue
| - Mutation leads to uncontrolled Ras activity
105
small G proteins
- associated with GPCR
- have intrinsic GTPase activity
- mutation can lead to cancer
- includes Ras, Rab, Rho, Arf, Ran
106
recognition domains for cell signaling
adapter proteins have SH2 or PTB domains that bind motifs on receptor that have phosphorylated Tyr
107
Fibrosarcomas in chickens
- Rous sarcoma virus causes fibrosarcoma in chickens
| - oncogenic viral-src is cause
108
restriction point of cell cycle
- arrested in G1 when growth factors limited
| - cell is independent of growth factors after restriction point
109
INK4
CKI specific for G1 CDKs
| -prevents association with cyclin D
110
CIP/KIP family of CKIs
bind G1 and S cyclin-CDKs
111
Cyclin E-CDK complex
active during G1-S phase
112
Cyclin D-CDK complex
active for G1 phase
113
Cyclin A-CDK and Cyclin B-CDK
initiates mitosis
114
Cyclin A-CDK
active for S phase
115
Wee1 kinase
inhibits cyclin-CDK by Phosphorylating Roof site
116
Cdc25 phosphase
activates cyclin-CDK by dephosphorylating roof site
117
p27
a CKI that controls G1/S CDKs and S-CDKs
118
APC/C
activated by binding to Cdc20
- ubiquitinates S and M-cyclins
- allows transition to anaphase
119
MDM2
keeps p53 inactive
120
intrinsic apoptotic pathway
mitochondria dependent
| BAX/BCL-2 key regulators
121
initiator caspases
caspase 8 and 9
| initiates apoptosis by activating executioner caspase
122
executioner caspases
caspase 3
| executes apoptosis
123
extrinsic apoptosis pathway
EC signals bind death receptors
- Fas and Fas Death receptor
- forms DISC which activates caspase 8 or 10 which activate executioner caspase 3
124
BAX protein
form pore in mitochondrial membrane following apoptotic signal
-releases cytochrome C
125
BCL-2
anti-apoptotic protein
| inhibits BAX aggregation
126
proto-oncogenes
- involved in signal transduction and execution of mitotic signals
- become oncogenes following gain of function mutation
- gene product that cause cell proliferation
127
Hallmarks of cancer cells
- produce own growth signals via oncogenes
- evade tumor suppressors
- activating invasion and metastasis
- replicative immortality, continued expression of telomerase
- inducible angiogenesis
- resist apoptosis
128
viral oncogenesis
- virus integrates host protooncogene into its genome
- mutations occur leading to oncogene
- new species of retrovirus capable of transforming host cell
129
Epstein-Barr virus
nasopharyngeal carcinoma
| Burkett lymphoma
130
Hep B virus
liver cancer
| hepatocellular carcinoma
131
HPV
cervical, uterine cancer
132
Kaposi sarcoma-associated herpesvirus
- observed in HIV patients
| - endothelial cells allowed to be transformed into tumor instead of destruction by immune system
133
MOA for Chemotherapies
- Alkylating agents
- Antimetabolites
- Topoisomerase I & II inhibitors
- Cytotoxic antibiotics
- Mitotic inhibitors
134
Homeodomain proteins and homeobox genes
regulate patterns of anatomical development
| -HOX gene
135
Hox genes
role in craniocaudal segmentation
136
Retinoic acid
regulates Hox gene expression
| -guides development of posterior embryo
137
Pax gene family
transcription factors
| -critical role in formation of tissues and organs
138
Dlx Genes
role in appendage patterns and jaw and inner ear
139
Msx genes
Prenatally- inhibitors of differentiation
| Postnatally- maintains proliferative capacity
140
T-box (Tbx) gene family
important for mesodermal layer development
| -also important for specifying forelimb vs hindlimb
141
Zinc finger proteins
involved in bone, cartilage development
- zinc deficiency results in skeletal growth retardation
- Sox genes are example
142
SoxA
same as SRY
143
WT1
Kidney and gonadal development
144
BMP4
If present = ectoderm become epidermis
| If blocked = ectoderm becomes neural plate
145
SHH
binds Patched which is bound to Smoothened
| regulates organogenesis, limb patterns and brain organization
146
tumor suppressor genes
limit frequency of cell division
147
Indirect ELISA
detects amount of antibody specific for antigen
148
sandwich ELISA
detects the quantity of antigen
149
short tandem repeats (STR)
varying repetitive regions of DNA between individuals
