Mutations + Cytoskeleton Flashcards
1
Q
Mutations
A
- heritable changes in DNA
2
Q
In single cell organisms, will all daughter cells have a mutation
A
Yes
3
Q
Somatic mutation
A
Mutation in a non-gamete
Passed to daughter cells in area
4
Q
Germ-line mutation
A
- mutation in sex cells
- passed onto new organisms - onto offspring
5
Q
Why are mistakes in transcription or translation not as critical
A
Many copies of RNA produced
RNA are not heritable over multiple generations
6
Q
What can cause mutations
A
- High intensity radiation
- chemical mutagens
- uncorrected mistakes in replication
7
Q
Proofreading in DNA
A
3’ to 5’ exonuclease activity in DNA polymerase (as in, it acts in the 3’ to 5’ direction) so it can backtrack.
8
Q
Mis Match repair system
A
- in E. coli, it scans recently synthesized DNA looking for mismatches and hemimethylated DNA )Methyl group added to an A in a GATC sequence in te replicated strand
9
Q
2 broad categories of mutation
A
Point
Chromosomal level
10
Q
Point mutations
A
- base substitution
- frameshift mutation
11
Q
Chromosomal level
A
- insertion/deletion
- inversion
- duplication
- translocation
12
Q
Transition
A
- when a purine is changed with a purine, and a pyrimidine with a pyrimidine etc
13
Q
Transversion
A
- when a purine is replaced with a pyrimidine and vice versa
14
Q
Missense mutation
A
- when in a coding region of DNA, the codon changes in one base an changes the amino acid that is coded for.
15
Q
Nonsense mutation
A
- when one base in a codon is changed to a stop codon in a coding region of DNA
16
Q
Same sense mutation
A
When a base in a codon is changed, but still codes for the same amino acid. (Will not notice mutation)
17
Q
Consequence of same sense mutations
A
- nucleotide changed to a different codon that specifies the same amino acid
- due to redundancy of codons
- no effect on protein/function
18
Q
Nonsense mutation consequence
A
- codon changes to a stop codon causing termination prematurely
- almost always causes an inactive protein
19
Q
Missense mutation consequences (incomplete)
A
- codon change to codon specifying another amino acid.
- if the amino acid wasn’t that important, or changes to a similar amino acid (with similar properties) then it will be at least partially functional.
- but if important, then protein will likely be inactive.
20
Q
Sickle cell Anemia mutation characteristics
A
- Glu to Val (number 6)
- caused by defective b globin subunit in hemoglobin protein
- single base pair sub changes charge of protein
- this causes hemoglobin protein to fold incorrectly
21
Q
Possible changes of codons
A
- same box - when you change 3rd base
- same column (horizontally) - when you change 2nd base
- same row (vertically) relative position - when you change 1st base
22
Q
Truncation
A
- premature appearance of stop codon
23
Q
Effect of an in frame removal of 3 bases
A
- one amino acid would be removed, rest of protein unaffected
24
Q
CF cause
A
- in frame deletion of PhenylAlanine codon at AA 508 of a 1400 AA protein
- Cl- accumulates in cells, causing thick mucus (due to water moving out of mucus)
25
Chromosomal level mutations
- insertion/deletion
- duplication
- inversion
-translocation (in relation to non homologous chromosomes)
26
Some lymphomas and leukemias caused by
- translocations
27
Many oncogenes are activated and become cancers though
- duplications
28
Fragile X syndrome and Huntington’s disease are also caused by
- duplications of short, repeated sequences
29
Infertility
- if inversions dont involve the loss of DNA they are often silent, but can cause this
30
Haemophilia A often caused by
Insertion mutations
31
Ames test for mutagenicity
- take mutated strain of bacteria that can’t grow without presence of histidine in one test tube, and in the other, add the suspected mutagen
- grow on plates without histidine
- incubate to allow growth
- might grow a colony or 2 - suggests that spontaneous mutations are the cause
- a large number of colonies in the one with suspected mutagen suggests that suspected mutagen is the thing that actually caused mutation.
32
Cytoskeleton
- dynamic system of protein fibers of various sizes
- can be reorganized as needed
- provides physical support and allows for movement.
33
Actin structure, and characteristics (G) (5)
- 43kDa protein made of 375 amino acids
- has nucleotide binding site that can accommodate ATP or ADP
- Has polarity directionally (Pointed or barbed)
- highly conserved protein
- very abundant
34
Components of cytoskeleton
- microtubules
- microfilaments
- intermediate filaments
35
Microtubules
- an tubulin
- 25nm outer diameter
36
How to actin monomers polymérisé
- in microfilaments
- adopts a helical shape
- prefer to add to the plus end
37
What does polymérisation of actin begin with
- nucleation
38
Nucleation
- G actin molecules randomly bump into each other
- actin binding molecules facilitate this
- forms dimers and trimmers
- nucleation is RDS
- non covalent, but stable interactions
- can add both ends and depolymerize at both ends, but favored at the plus end (adding) and dépolymérisation favored at the minus end.
39
Actin polymérisation
- ATP bound actin ahs higher affinity for other actins
- when actin binds to other actin, ATP hydrolyses to ADP
40
Actin microfilaments assembled in 3 ways
- actin bundles
- actin networks
- actin contractile elements
41
Actin bundles
- can form microvilli (actin bundles stabilise this extension of the cytoplasm) which increase surface area by 10-20x time
42
Actin networks
- provides structural stability but are more flexible than bundles
- actin binding protein link filaments together.
- eg terminal web under the plasma membrane
43
Myosin
Converts chemical energy to mechanical energy (kinetic) which generates force and movement
44
Actin and myosin responsibilities examples
- cell division
- cell crawling
- some vesicle movement
- muscle contraction
45
What cancels do with a combination of actin and myosin
- cytokinesis - contractile ring of actin with myosin fibers
- cell crawling
- vesicle movement
46
Level of organisation of muscle fiber
- tissue - bundle of muscle fibers - muscle fiber - myofibrils- sarcomere
47
I band
- area of only actin
48
Z line
2 Z lines = sacromere
49
H zone
- myosin area only
50
A band
- area of overlap of myosin and actin fibers
51
M line
- middle of sarcomere
52
Microtubules
- guides intracellular transport
- segregating chromosomes during mitosis
- propulsion or sweeping of fluids over membranes
53
Microtubule material
- tubulin
54
A tubulin
- had GTP binding site
55
B tubulin
- has GTP binding site, but gets hydrolyzed to GDP during polymerisation
56
Tubulin polymerization
- 13 linear protofilaments surrounding a hollow core
- assembled head-to-tail so Microtubule has polarity
57
Microtubule behavior influence by drugs
- binding tubulin
- binding Microtubule
58
Binding tubulin drugs
- induces polymerisation at 2 things: Nonspecifically affects all MTs, and Targets rapidly dividing cells
- (Non specific) : Colchicine and Colcemid
- (Rapdily dividing cells: vincristine)
59
Binding Microtubule drugs
- stabilises Microtubules
- targets rapidly dividing cells
- eg taxol
60
IN vivo, what happens to tubulin dimers
- most polymerisation and dépolarisation happens at plus end.
- because minus end has something on it
61
Where do new microtubules come from
- Microtubules organizing centres (MTOC)
- primary MTOC is centrosome in animal cells
62
Centrioles
9 triplet arrangements of microtubules of A.B,C microtubules
63
Pericentriolar material
- Amorphous collection of protein from which MTs emanate
- gamma tubulin present for efficient Microtubule formation in the PCM.
64
True or false; MTs originate in the centrosome but stay there
False - stable microtubules can be removed and placed into other parts of the cell.
65
Microtubules motor protein
Kinesin - move toward the plus end
Dyneins - move toward the minus end of the Microtubule
66
Functions of microtubules and associated motor proteins
- Intracellular vesicle transport
• Organelle movement and positioning
• Color changes
• Bending of cilia and flagella
• Separation of sister chromatids and centrosomes during
M-phase
67
Axoneme
- 9+2 arrangement (9 doublets + an extra pair)
- unit of function in cilia or flagellum
- central pair is NON connected and complete 13 protofilaments (the extra pair)
- radial spoke proteins
- nexin links connect outer doublet microtubules
68
Basal body
- minus end of axonene MTs anchored in a basal body
69
Duchenne’s muscular dystrophy caused by
A deletion mutation
