Chapter 15 Gene Mutation, DNA Repair, and Transposition Flashcards
1
Q
A ________ is an alteration in gene sequence
A
mutation
2
Q
A mutation is any base pair change in sequence.. (T/F)
A
True
3
Q
A mutation can be a single base pair substitution (T/F)
A
True
4
Q
A mutation can be a deletion or insertion of base pairs (T/F)
A
True
5
Q
A mutation can be a major alteration in chromosomal structure (T/F)
A
True
6
Q
Mutations may occur in somatic or germ cells. (T/F)
A
True
7
Q
Mutation may occur in coding or noncoding regions (T/F)
A
True
8
Q
Mutations are source of new alleles and orgin of new genetic variation (T/F)
A
True
9
Q
_____ mutations: one base pof tripair is altered
A
point
10
Q
__________ mutations:
- insertion or deletion
- loss or addition of nucleotide causes shift in reading frame
- frame of triplet reading during translation is altered
A
Frameshift
11
Q
______ mutation:
- alters a codon
- no change in the amino acid
- example: GGU to GGC
A
silent
12
Q
__________-
- pyrimidine replaces a pyrimidine
- purine replaces a purine
- nucleotides are ???
A
transition
13
Q
___________-
-purine and a pyrimidine are interchanged
A
transversion
14
Q
____ of ________ mutation:
reduces/ eliminates function of gene product
A
loss of function
15
Q
____ mutation:
results in complete loss of function
A
null
16
Q
________ mutation :
results in mutant phenotype in diploid organism
A
dominant
17
Q
________ ____ of ________:
results in gene with enhanced, negative, or new function
A
dominant gain of function
18
Q
______ mutation:
- interrupt an essential process
- result in death
- amino acid
- ex: tay- sachs
A
lethal
19
Q
___________ mutation:
- enviornment
- temperature- sensitive mutation
A
conditional
20
Q
_______ mutation:
- occurs in protein- coding region or in any part of genome
- majority of mutations occur in noncoding region
- mutate to a chemically similar
- effect on genetic fitness of organism is neither beneficial nor detrimental
A
neutral
21
Q
_______ mutations:
occur in any cell except germ cells; are not heritable
A
somatic
22
Q
____ ____ mutations:
occur in gametes; are inherited
A
germ line
23
Q
_________ mutations:
occur within genes located on autosomes
A
autosomal
24
Q
_ ______ and _ ______ mutations:
occur within genes located on x and y chromosome, respectively
A
x linked and y linked
25
_________ _________ mutation:
- occurs in somatic cell of diploid organism
- is unlikely to result in detectable phenotype
recessive autosomal
26
_________ ________ mutation:
| are expressed phenotypically in first generation
inherited dominant
27
_ _______ _________ mutations:
- arise in gametes of homogametic female
- may be expressed in hemizygous male offspring
x linked recessive
28
mutations are either spontaneous or induced (T/F)
True
29
___________ mutation:
- changes in nucleotide sequence that occur naturally
- arise from normal biological or chemical processes that alter nitrogenous bases
spontaneous
30
________ mutations:
- result from influence of extraneous factors, either natural or artificial
- radiation
- uv light
- natural and synthetic chemicals
induced
31
spontaneous mutation rates at variious loci in different organisms:
- low for all organisms
-rate varies between organisms
-within species, rate varies from gene to gene
(T/F)
True
32
S. Luria and M. Delbruck- direct evidence that mutations do/ do not occur as an adaptive mechanism???
do not
33
```
Luria- Delbruck Fluctuation Test:
Grew several e coli liquid cultures
added e coli to plates + T1 bacteriophage
which cells were lysed?
T/F
```
True
34
Luria- Delbruck Fluctuation Test:
Hypothesis 1: adaptive mutation
-little fluctuation in number of resistant cells from plate to plate
Hypothesis 2: spontaneous mutation
-mutations occur in a low rate prior to plating
-early during incubation, result in large # of resistant cells
-Late in incubation, fewer resistant cells
(T/F)
True
35
```
SPONTANEOUS MUTATIONS ARISE FORM REPLICATION ERRORS AND BASE MODIFICATIONS:
-DNA replication errors
-Replication slippage
-Tautomeric shifts
-Depurination and deamination
-oxidative damage
-transposons
(T/F)
```
True
36
Spontaneous mutations arise from replication errors (T/F)
True
37
Replication Slippage:
-if ________ occurs in template strand during replication, DNA polymerase misses looped out nucleotides, and _________________ and deletions occur
-More common in repeat sequences (hot spots)
hot spots for DNA mutation
contribute to hereditary diseases
LOOK UP
38
TAUTOMERIC SHIFTS
-Exist in alternate chemical forms- tautomeric forms
-single proton shift
-hydrogen bonding with non- complementary bases
-results: unusual base pairing lead to mutations
(T/F)
True
39
DEPURINATION AND DEAMINATION
-DNA base damage is the most common cause of spontaneous mutation
-Depurination- loss of a nitrogenous base; leading to an apurinic site (without purine)
-not repaired- polymerase introduces random nucleotide
-deamination- amino group in cytosine or adenine is converted to a keto group
(T/F)
True
40
DEAMINATION OF CYTOSINE AND ADENINE:
-cytosine is converted to uracil, which base pairs with adenine
-adenine is converted to hypoxanthine, with base pairs with cytosine
-spontaneous or result of chemical mutagens (nitrous acid)
(T/F)
True
41
OXIDATIVE DAMAGE
| DNA damage by the by- products of normal cellular processes. (_______ respiration)
aerobic
42
OXIDATIVE DAMAGE
| exposure to high- energy radiation (T/F)
True
43
OXIDATIVE DAMAGE
| include: superoxides, hydroxyl radicals, and hydrogen peroxide (T/F)
True
44
OXIDATIVE DAMAGE
| lead to DNA mispairing loss of bases, and single strand breaks (T/F)
True
45
```
TRANSPOSONS
-naturally occuring mutagens
-transposable genetic elements
-move in or between genes
-cause inversions, translocations, double- stranded breaks- create chromosomal damage
(T/F)
```
True
46
what if dna element is inserted into regulatory region of a gene?
disrupt proper expression of a gene after reading from or introduce stop codons
47
INDUCED MUTATIONS
| ________- natural or artificial agents that induce mutations
mutagens
48
```
INDUCED MUTATIONS
-all cells are exposed to plethora of mutagens
-fungal toxins
-cosmic rays
-uv light
-industrial pollutants
-medical x rays
-chemicals in tobacco smoke
(T/F)
```
true
49
BASE ANALOGS
-substitute during DNA replication
-5-bromouracil: derivative of uracil, thymine analog, halogenated at 5th position
-increases probability tautomeric shift
-increases uv light sensitivity
-2 amino purine: analog to adenine, thymine or cytosine
(T/F)
True
50
ALKYLATING AGENTS
| Donate to _____ group (CH3 or CH3CH2) to amino or keto groups in nucleotides
alkyl
51
ALKYLATING AGENTS
alters base pairing affinity; transition mutation
ex: mustard gases
(T/F)
true
52
INTERCALATING AGENTS
-frameshift mutations
ex. proflavin, acridine orange, ethidium bromide
-intercalates: wedge themselves between nucleotides
-chemicals with dimensions and shape that wedge between DNA base pairs
-this causes base pair distortions and DNA unwinding
(T/F)
True
53
ADDUCT- FORMING AGENTS
-mutation causing chemicals
-covalently binds to DNA, altering conformation and interfering with replication and repair
(T/F)
True
54
ADDUCT FORMING AGENTS
| Acetaldehyde: component of _________ smoke
cigarette
55
ADDUCT FORMING AGENTS
Heterocyclic amines (HCA's):
-cancer causing chemicals created during cooking of meats
-17 different HCA's are linked to cancers of stomach, colon, and breast
(T/F)
True
56
UV LIGHT-
electromagnet spectrum
purines and pyrimidines absorbs uv light at 260 nm
(T/F)
True
57
```
PYRIMIDINE DIMERS
-uv radiation
-two identical pyrimidines
-distort DNA conformation
-inhibit normal replication
-errors introduced during replication
(T/F)
```
True
58
IONIZING RADIATION
-energy of radiation varies intensely with wavelength
-x rays, gamma rays, and cosmic rays
-rays penetrate deeply into tissues
-molecules are transformed into free radicals
-break phosphodiester bonds, leading chromosomal abnormalities
(T/F)
True
59
FREE RADICALS
-stable molecules transformed into free radicals (chemical species containing one or more unpaired electrons)
-free radicals directly/ indirectly affect DNA
(alters purines and pyrimidines, break phosphodiester bonds, produce deletions, translocations, and fragmentation)
(T/F)
True
60
HUMAN DISEASES DUE TO MUTATIONS
| POLYGENIC: most human genetic diseases are polygenic, caused by variations in _______ genes
several
61
HUMAN DISEASES DUE TO MUTATIONS
MONOGENIC: single base pair change in one of approximately 20000 human genes may lead to serious inherited disorders
(T/F)
True
62
SINGLE GENE MUTATIONS
30% of mutations causing human diseases are single base-pair mutations creating ________ mutations
-PREMATURELY TERMINATE PROTEIN SYNTHESIS
-TRIGGER RAPID DECAY OF MRNA
nonsense
63
SINGLE GENE MUTATIONS
________/ __________ mutations- alter protein sequence and create internal nonsense codons
-15% point mutations that cause genetic diseases are from abnormal mRNA slicing
missense/ nonsense
64
B- THALASSEMIA
arise from a large number of mutations
-over 250 mutations in the B-globin gene
(single nucleotide change or insertions/ deletions, 1.6 kilobases DNA; code 146 amino acids, 20 common mutations)
-autosomal recessive blood disorder resulting from a reduction or absence of hemoglobin
-varying degrees of anemia
-severe to mild symptoms; weakness, delayed development, jaundice, and enlarged organs
-most common dingle gene disease in the world
(T/F)
True
65
TRINUCLEOTIDE REPEAT
short DNA sequences found in mutant genes
normal individuals may have a low number of repitions
individuals with over 20 disorders exhibit over 200 repeats
fragile x syndrome
huntington disease
myotonic dystrophy
(T/F)
True
66
DNA REPAIR
repair systems counteract spontaneous and induced DNA damage
-DNA repair system: maintains integrity of genetic material
-repair systems counteract genetic damage that would result in genetic diseases and cancer
(T/F)
True
67
DNA REPAIR SYSTEMS
Proofreading:
-DNApolymerase III- 3'-5' exonuclease activity
-removes and replaces incorrectly inserted nucleotides
-what corrects errors that remain???
________ repair
mismatch
68
DNA REPAIR SYSTEMS
mismatch repair:
-mismatches are detected, cut and removed (exonuclease and endonuclease)
-correct nucleotide inserted by DNA polymerase
(T/F)
True
69
DNA REPAIR SYSTEMS
correct DNA strand is recognized based on strand discrimination
DNA methylation of the parental strand
(T/F)
True
70
DNA REPAIR SYSTEMS
DNA METHYLATION:
-adenine methylase (enzyme in bacteria)
-recognizes 5'-GATC-3' during DNA replication
-adds methyl groups to adenine residue
-newly synthesized strand of replication remains unmethylated
-repair enzymes recognizes unmethylated strand and repairs mismatch
(T/F)
True
71
POSTREPLICATION REPAIR
-DNA replication skips over a lesion
-responds after damaged DNA has escaped repair and has failed complete replication
-RecA protein directs recombination exchange with corresponding region on undamaged parental strand (donor DNA)
-Undamaged segment of DNA replaces gap
(T/F)
True
72
SOS REPAIR SYSTEM
-E. Coli
-last resort to minimize DNA damage
-DNA synthesis becomes error prone ; inserts random/ incorrect nucleotides in places that normally would stall replication
-bacteria induce expression of 20 genes; their products allow replication to move forth
-SOS repair can itself become mutagenic; allows cells to survive with DNA damage (cell would otherwise kill itself)
(T/F)
True
73
PHOTOREACTIVATION REPAIR
-Cleaves bonds between thymine dimers reversing effect of UV radiation
-Process depends on photoreactivation enzyme (PRE)
-cleaves thymine dimer bonds in presence of light... why???? for PRE to be activated, it has to absorb proton of light
(T/F)
True
74
```
BASE AND NUCLEOTIDE EXCISION REPAIR
-light independent DNA repair mechanisms exist in all prokaryotes and eukaryotes and involve exision repair
-excision repair involves three steps:
1.removal of the mutation by a nuclease
2.gap filled by DNA polymerase
3.sealing of the nick by DNA ligase
(T/F)
```
True
75
BASE EXCISION REPAIR
-recognition of the erroneous base by DNA glycosylase
-creates apyrimidinic or apurinic site
-cutting of the DNA backbone by AP endonuclease
-distortion in helix; corrected by excision repair
-mutations: sensitive to gamma rays and oxidizing agents
(T/F)
True
76
```
NUCLEOTIDE EXCISION REPAIR
-repairs bulky lesions
-uvr genes (ultraviolet repair)
-in e. coli around 14 nucleotides are removed
-DNA pol 1 and DNA ligase
-opposite strand used as template
(T/F)
```
True
77
CONNECTING CONCEPTS- BASIC PATHWAY OF DNA REPAIR
1. detection- damaged DNA is recognized
2.excision- DNA is nicked; nucleotides removed
3.polymerization- DNA pol adds nucleotides to 3' OH; uses other strand as a template
4.Ligation- DNA ligase
(T/F)
True
78
GENETIC DISEASES ASSOCIATED WITH DEFECTS IN DNA REPAIR
xeroderma pigmentosum (XP)
-sensitivity to sunlight
-developmental and neurological disorders
-individuals have 2000 fold higher rates of cancer
-defects in NER
-30 genes
-autosomal recessive
(T/F)
True
79
AUTOSOMAL RECESSIVE DISEASES DUE TO DEFECT IN NER PATHWAY
Cockayne syndrome (CS)
-developmental and neurological defects
-sunlight sensitivity but no increase in cancers
-premature aging, with death by 20
DEFECTS IN NER
(T/F)
True
80
AUTOSOMAL RECESSIVE DISEASES DUE TO DEFECT IN NER PATHWAY
Trichothiodystrophy (TTD)
-dwarfism, retardation, brittle hair and skin
-facial deformities and sensitivity to sunlight
-no increase in cancers- six year life span
DEFECTS IN NER
(T/F)
True
81
```
AMES TEST
Salmonella typhimurium
-increased sensitivity to mutagens
-mutation type can be determined
-base pair mutations
-frame shift mutations
(T/F)
```
True
82
```
AMES TEST
His operon mutation
-His- unable to synthesize His
-Requires His for growth
(T/F)
```
True
83
AMES TEST
Test measure frequency of reverse mutations
Many known carcinogens have been shown by the Ames test to be strong mutagens (i.e. compounds in cigarettes)
(T/F)
True
84
TRANSPOSITION
First evidence- Barbara McClintock's breeding experiments with Indian corn
Transposable element from one location to another
Insert themselves into various within genome
Several mechanisms used in prokaryotic and eukaryotic cells
common features:
-staggered breaks made in target DNA
-Transposable element is joined to ss ends of target DNA
-DNA is replicated at the ss gaps
(T/F)
True
85
TRANSPOSABLE ELEMENTS
What are transposable elements???
-Transposons
-move within the genome
-insert themselves into various positions within and between genes
Insertion sequences and bacterial transposons
(T/F)
True
86
INSERTION SEQUENCES
simplest
vary up to 2000 bp, present in multiple copies in genome
transposase gene and inverted terminal repeats
recognized by enzymes that catalyze
(T/F)
True
87
```
BACTERIAL TRANSPOSONS
larger than IS elements
consist of protein encoding genes unrelated to transposition
can introduce multiple drug resistance to bacterial plasmids; move from plasmids to bacterial chromosomes, spreading multiple drug resistance between strains
some tn elements
-short inverted repeats
-transposase gene
(T/F)
```
True
88
MAIZE
Barbara McClintock
identified changes in color of corn kernels
postulated that some genetic elements move from other genome locations into the genes for kernel color
2 transposable elements Ac(activator) and Ds(dissociation) elements
range of pigment variations in corn kearnels
awarded the nobel prize in 1983
(T/F)
True
89
COPIA ELEMENT
copious amounts of RNA; present 10-100 copies
5000-8000 base pairs of DNA
Long direct terminal repeawts (DTR's) at each end
inverted terminal repeat (itr)
dispersed throughout genome and transposable to different chromosomal locations
eye color and segment formation
(T/F)
True
90
P ELEMENTS
drosophilia
DNA transposon with terminal inverted repeats
0.5-2.9 kb of DNA
demonstrated in hybrid dysgenesis
high rates of transposition
encode a transposase and a repressor protein that inhibits transposition
transposase gene is expressed only in germ line
-tissue specific
(T/F)
True
91
TRANSPOSABLE ELEMENTS IN HUMANS
LINES and SINES are major families of human transposons
up to 34% human genomic DNA
Generate mutations leading to human disorders
Alu insert into BRCA2 gene, resulting in breast cancer
Dystrophin- different transposons, can lead to muscular distrophy
hemophilia
(T/F)
True
