Chapter 7

Question 1

Mutations?

Answer 1

Heritable changes in the base pair sequence of DNA

Question 2

Forward Mutation

Answer 2

Changes in wild-type allele to a different allele (A+–>a)

Question 3

Reverse Mutation (reversion)

Answer 3

Changes a mutant allele back to wild-type (a–>A+)

Question 4

Substitution

Answer 4

Replacement of a base by another:
Transition: purine replaced by another purine
Transversion: Purine replaced by a pyridimine (vice versa)

Question 5

Deletion

Answer 5

block of one more more base pairs lost from DNA

Question 6

Insertion

Answer 6

Block of one or more base pairs added to DNA

Question 7

Point Mutations

Answer 7

Affect one or a few base pairs, alternate one gene at a time.
Can include transitions, transversions, small deletions or insertions

Question 8

Rates of Mutations

Answer 8

Different genes have different rates.
Rates higher in gamete producing eukatyotes (meiosis)

Question 9

Human MutationRates

Answer 9

Rate = 1x10-8
Every child has approx 60 mutations - most do not affect phenotype
Higher rate in sperm (2^-4 x 10^-8) - more mitosis

Question 10

Are Revertants more or less rare than Forward Mutations?

Answer 10

Revertants are MORE RARE than forward mutations

Question 11

Luris-Delbruck Fluctuation Experiment

Answer 11

Bacterial resistance arises from mutations that occured before exposure to bactericide.
- allows survival of cells with pre-existing resistance
Mutations are random and heritable

Question 12

Depurination

Answer 12

Natural process
Hydopusis of purine base
1000/hr in every cell

Question 13

Deamination

Answer 13

Natural
Removal of amino group
C to U
normal C-G –> A-T after replication

Question 14

Cosmic and X-rays

Answer 14

Natural
break sugar-phosphate backbone
UV- thymine diamers

Question 15

Oxidative Damage

Answer 15

Natural
8-oxodG mispairs with A
G-C –> mutant Y-A after rep

Question 16

How do Cells Decrease Replication Mistakes

Answer 16

Proofreading:
Portion of DNA polymerase called 3’-5’ exonuclease can recongnize and remove mismatches

Question 17

Tautomerization

Answer 17

Results in replication mistakes
-each base has 2 tautomers that can interconvert and cause incorrest base matching

Question 18

Trinucleotide Repeats

Answer 18

20 human disease genes have unstable trinucleotide repeats (huntingtons)
- children have an expanded number

Question 19

Trinucleotide Cause

Answer 19

Expansion and contraction occur by slipped mispairing

Question 20

Mutagens

Answer 20

Agents that raise frequency of mutations above spontaneous rate

Question 21

H.J. Muller Experiment

Answer 21

Used X-ray on male flies and was able to determine that it raised the mutation rate

Question 22

How Mutagens Alter DNA: Base Replacement

Answer 22

Replace a base - base analogs - chem structure almost identical to normal base

Question 23

How Mutagens Alter DNA: Hydroxylation

Answer 23

alter base structure and properties - adds an OH
C matches with A not G

Question 24

How Mutagens Alter DNA: Alkylation

Answer 24

Alters base structure and properties - alkylating agents add ethyl or methyl groups
G matches with T not C

Question 25

How Mutagens Alter DNA: Deamination

Answer 25

alter base structure and properties - deaminating agents remove amine groups

Question 26

How Mutagens Alter DNA: Insertion

Answer 26

Insert between bases - intercalators proflavin can cause base insertion and deletions

Question 27

Somatic Mutations

Answer 27

In non-germ cells not heritable can affect to survival and lead to cancer

Question 28

Ames Test

Answer 28

Used to determine if chemicals are carcinogens by testing Histidine Many HIS- ---> HIS+ = bad

Question 29

Base Excision Repair

Answer 29

1. DNA glycosylase removes altered N base 2. Nearby nucleotides removed 3. New DNA synthesized to fill gap important for removing U caused by deamination

Question 30

Nucleotide Excision Repair

Answer 30

1. UvrA + UvrB complex scans for distortions to double helix (thymine diamers) 2. UvrB + UvrC complex cuts around the damaged DNA 3. DNA polymerase fills the gap

Question 31

Double Stand Break Repair

Answer 31

Homologous Recombination: - similar to meiosis Nonhomologous end-joining - repair of double-strand breaks

Question 32

Bacteria: methyl-directed mismatch repair

Answer 32

Corrects mistakes in replication -MutS and MutL bind to mismatched nucleotides - MutH cuts unmethylated strand Opposite methylated - gap made in new strand by DNA exonuclease - gap filled by DNA polymerase using old strand template

Question 33

Error Prone DNA Repair Mechanisms

Answer 33

SOS system - Bactria - used at rep forks that stalled because of unrepaired damage - bad DNA polymerase used - adds random nucleotides Microhomology Mediated End-joining (MMEJ) - similar to NHEJ but nucleotides are removed at double- stranded breaks --> small deletions

Question 34

Examples of Hereditary Human Diseases Due to Defects in DNA Repair

Answer 34

- Xeroderma Pigmentosum -Hereditary colorectal cancer - Hereditary forms of Breast Cancer - BCRA1 + BCRA 2

Question 35

Why are Mutations Important

Answer 35

to respond to changes in the environment, would die out without mutations