29 Mutation, Mutagens, and Repair Mechanisms Flashcards
1
Q
somatic mutations
A
transmitted to daughter somatic cell through mitosis
2
Q
Results in clone of cells with the mutation but not present in all somatic cells and not passed to offspring
A
somatic mutation
3
Q
germ-line mutation
A
passed through the gametes
4
Q
Results in all progeny having the mutation
A
germ-line mutation
5
Q
Mutations at the protein level…
A
result in a loss of function or a gain of function
6
Q
Loss of function
A
- recessive mutations
- partial or complete lack of protein function due to the mutation
7
Q
Gain of function
A
- cell makes a protein that it would not normally make could be due to new gene product at a time or place when it would not normally be made
- dominant typically
8
Q
point mutation
A
- results in substitution of 1 base pair (not just base) for another
9
Q
point mutations at the DNA level can be classified as…
A
transition
transversion
10
Q
transition
A
point mutation
purine to purine or pyrimidine to pyrimidine
11
Q
transversion
A
point mutation
pyrimidine to purine or purine to pyrimidine
12
Q
simplest type of mutation
A
point mutation
13
Q
AT base pair changes to GC
A
transition
14
Q
AT base pair changes to CG
A
transversion
15
Q
A base pair is always written with the ___ strand and then the ___ strand
A
coding then template
16
Q
AT to TA
A
transversion
17
Q
CG to TA
A
transition
18
Q
GC to TA
A
transversion
19
Q
purines
A
AG
20
Q
pyrimidines
A
CT
21
Q
Effects of point mutation at the protein levels
A
- missense
- neutral
- nonsense
- synonymous
- readthrough
22
Q
nonsynonymous
A
the mutation alters the amino acid sequence of the protein
23
Q
missense
A
when a nonsynonymous mutation alters the protein function or results in a nonfunctionalprotein
24
Q
neutral
A
a nonsynonymous mutation in which the amino acid sequence is altered but the protein function stays the same
25
nonsense
a mutation alters a codon so that it becomes a stop codon causing premature termination of translation
26
synonymous
- aka silent
- a point mutation alters the codon but the new codon still codes for the same amino acid
- because the code is degenerate
27
readthrough
a mutation causes a stop codon to change to one that codes for an amino acid resulting in a longer protein
28
reverse mutation
a mutation that "undo" the original mutation
- exact reversion
- equivalent reversion or suppressor mutation
- intragenic
- intergenic
29
exact reversion
the normal codon is put back into position
30
equivalent reversion
aka suppressor mutation
restores the normal phenotype but the DNA is not exactly the same
31
intragenic
occurs within the same gene as the original mutation
32
intergenic
occurs in a different gene but allows normal phenotype
33
depurination
results in an apurinic site
removes glycosidic bond at either G or A bases
34
deamination of C
results in uracil
causes GC to AT transition
35
wobble base pairing
mispairing due to flexibility in helix
results in transitions after replication
36
after second round of replication, depurination results in...
a transition or transversion
37
after one round of replication in deamination of cytosine
the strand with normal guanine picks up a cytosine and is normal
the strand with uracil pick sup an adenine
38
after second round of replication in deamination of cytosine
the adenine of the strand with uracil pairs with thymine to complete the transition
the uracil again pairs with adenine if it is still present, though it may have been repaired
39
How many rounds are needed to make both strands undergo transition in wobble base pairing
two rounds
40
frameshift mutation
occurs when one or more base pairs of DNA are inserted into the gene
shifts the reading frame of all codons moving forward
can alter start and stop sites
41
unequal crossing over
can cause insertions and deletion
homologous chromosomes do not line up precisely causing one recombinant product to have an insertion and one to have a deletion
42
template slippage
model for spontaneous mutation
- in area with repeat sequence
- during replication a segment slips out
- the remaining sequence is held together as there are other copies of the sequence to base pair with the non-slipped strand
- after next round of replication the new double helix will be 2 base pairs shorter
43
Frameshift mutations are more likely to occur...
in areas where a repeated sequence is present in the DNA
44
expansion of repeats
- may occur during hairpin formation during replication
- hairpin formation within the area that slips out may provide stability of the slipped out structure and can lead ot an increase in repeated segments form generation to generation
45
Fragile X syndrome
an example of expansion of repeats
due to expansion of a trinucleotide repeat of CGG near the tip of the long arm of the X chromosome
46
Fragile X syndrome symptoms
range from moderate learning disability to severe intellectual disability, behavior and attention problems, and autistic behaviors
47
anticipation
disorder shows earlier and more severe symptoms in successive generation
48
anticipation in Fragile x
increased symptoms result from increased number of repeats, number of repeats increase from generation to generation
49
examples of disorders due to extra copies of a trinucleotide repeat
Huntington's
| fragile x
50
mutagen
an agent that causes mutation to occur at a rate greater than the spontaneous rate
51
agents of chemically induced mutations
- base analogs
- alkylating agents
- deamination
- hydroxylamine
- oxidative reactions
- intercalating agents
52
examples of mutagens
chemicals, UV light, x-rays, ethidium bromide, etc
53
base analogs
structures similar to base structures
can be incorporated into the DNA during replication if present
mispair more frequently than normal bases
require 2 or more rounds to obtain
always transitions
54
ex of base analogs
5-bromouracil
| 2-aminopurine
55
5-bromouracil
usually pairs with adenine but can also with guanine
56
2-aminopurine
normally pairs with thymine but can also with cytosine
57
alkylating agents
ex EMS
| donate ethyl and methyl groups causing mispairing
58
deamination mutation
ex nitrous acid
causes deamination of C, A, G causing transitions
59
hydroxylamine
changes cytosine to uracil causing mispairing
60
aflatoxin
causes GC to TA transversion
first causes apurinic site for guanine
then during replication it causes adenine to be put across from missing base
in next round, adenine will pair with thymine completing the transversion
61
example of mutagen that causes transversion
aflatoxin
| oxidating agents
62
oxidating agents
ex 8-oxyguanine
- causes GC to TA tranversions
- oxidative reaction converts guanine to 8-oxyguanine which pairs with adenine during replication
in next round the adenine pairs with thymine
63
intercalating agents
large planar molecules can slide between the base pairs to cause frameshift mutations
cause distortion in the helix leading the template slippage during replication
64
ex of intercalating agents
proflavine
acridine orange
ethidium bromide
65
common structure of intercalating agents
several ring structures joined together making them flat and planar in shape
66
x-rays
lead to chromosome aberrations by breaking the phosphodiester bonds
can also damage bases and cause point mutations
67
x-rays do most damage in...
dividing cells
68
pyrimidine dimer
- formed due to UV light causing covalent bonds between two adjacent pyrimidines on the same strand of dsDNA
- distort helix and inhibits replication
69
pyrimidine dimers can be between...
2 thymines
2 cytosines
a thymine and a cytosine
70
pyrimidine dimers typically lead to...
cell death
if cell survives, mistakes will be made in replication since bases involved in dimer cannot be used as a template for replication
71
direct repair mechanism
used to correct the structure of an abnormal nucleotide without replacing the nucleotide
72
photoreactivation repair of pyrimidine dimers
- ex of direct repair mechanism
- the enzyme photolyase binds the dimer and absorbs a photon of blue light, then clips the dimer. the enzyme is then released restoring the normal DNA sequence
73
methyltransferase
example of direct repair mechanism
restores correct form to incorrectly methylated guanine bases
removes methyl groups from incorrectly methylated guanine bases restoring the normal base structure and allowing normal base pairing to occur in the next round of replication
74
proofreading during replication
- if the improper nucleotide is added in replication the 3'OH is not in right place for addition of next nucleotide
DNA polymerase stalls replication, exonuclease removes incorrect nucleotide, then DNA polymerase inserts the correct nucleotide
75
After proof reading, replication errors are about...
1 in 10 million nucleotides
76
Mismatch repair
designed to identify improperly paired base pairs and remove them
- happens in situations where proofreading misses the incorporation error
77
mismatch repair process
- the mismatch repair complex recognizes the abnormal helical structure and identifies the incorrect base
- complex binds near the site
- exonucleases clip the sugar phosphate backbone of the new strand to remove an area that includes the mismatch
- dna polymerase fills the gap
- ligase seals the nick
78
how is the mismatch repair complex able to recognize the old vs new strand?
the old strand is methylated, the new is not
79
Nucelotide excision repair is for...
bulky lesions such as pyrimidine dimers
80
nucleotide excision repair
- repair many types of dna damage in pro and eukaryotes
81
nucleotide excision repair process
- enzyme complex recognizes the distortion in the helix
- the strands of dna are separated and held apart by single strand binding proteins
- the enzyme cleaves the sugar phosphate backbone on both sides of the lesion removing several nucleotides including the defective area
- dna polymerase fills in the gap and ligase seals the nick
82
UVR endonuclease
enzyme that recognizes distoration due to pyrimidine dimers for nucleotide excision repair
83
base excision repair of modified bases
removes the defective base and then the rest of the nucleotide and then fills in the DNA correctly
84
base excision repair process
- glycosylase recognizes and removes defective base
- the rest of the nucleotide is still present causing a apurininc or apyrimidinic site
- the AP endonuclease enzyme cleaves the phosphodiester bond next to the missing base causing a nick and removes the rest of the nucleotide
- DNA polymerase can then fill in the gap and ligase can seal the nick
85
glycosylases are specific to...
a specific modified nucleotide so there are separate ones for uracil, hypoxanthine, 7-methylguanine, etc.
86
DNA repair plan of attack
1. detection of damaged area of DNA
2. excision of damaged section
3. polymerization - gap filled by polymerase
4. ligation of final nick in the backbone of DNA
87
DNA repair processes differ in...but all use...
differ in how the detection and excision occur
all use DNA polymerase to fill in gaps and ligase to fill the nicks
88
methods of double strand break repair
homologous recombination repair
nonhomologous end joining
89
double strand break
breaks in both strands of the DNA
can lead to inversion, translocations, deletions, and duplications
90
homologous recombination repair
uses the sister chromatid to provide a template for repairing the break
similar to the mechanism for crossing over
91
two enzymes important in homologous recombination repair
the products from the BRCA1 and BRCA2 genes
92
nonhomologous end joining
allows repair when sister chromatid is not available
proteins recognize the broken ends and join them together
more error prone then homologous recomb repair and often leads to chromosome aberrations
93
when may nonhomolgous end joining be useful
during G1 when no sister chromatid is available
94
translesion DNA polymerases
specialized polymerases that can bypass lesions on the DNA during replication
often make errors
allow replication to proceed at the cost of introducing mututation
95
Xeroderma pigmentosum
due to faulty nucleotide excision repair of pyrimidine dimers
there are various mutations in several genes which result in this
96
Xeroderma pigmentosum symptoms
very sensitive to sunlight
high risk of skin cancer since many pyrimidine dimers do not get repaired
