Lecture 14 Mutations and Repair Ch. 18

Question 1

What are the two major categories of mutations?

Answer 1

Somatic and Germ-line

Question 2

Somatic mutations arise where?

Answer 2

In tissues other than those that produce gametes

Question 3

What mutations are restricted to the individual?

Answer 3

Somatic mutations

Question 4

Germ-line mutations arise where?

Answer 4

In tissues that produce gametes

Question 5

What mutations can be passed to offspring?

Answer 5

Germ-line mutations

Question 6

What are transition mutations?

Answer 6

Base substitutions: Purine replaced by purine; pyrimidine replaced by pyrimidine

Question 7

What are transversion mutations?

Answer 7

Base substitutions: Purine replaced by pyrimidine or vice versa

Question 8

What are the types of frameshift mutations?

Answer 8

Insertions, and deletions

Question 9

Describe forward mutations

Answer 9

Mutation that alters the wild-type phenotype

Question 10

Describe reverse mutation

Answer 10

Mutation that changes the mutant phenotype back into the wild-type

Question 11

Describe missense mutations

Answer 11

Base substitution that changes the sequence and the meaning of a mRNA codon, resulting in a different amino acid being inserted into a protein

Question 12

Describe nonsense mutation

Answer 12

Mutation that changes a sense codon into a termination codon

Question 13

Describe silent mutation

Answer 13

Mutation that changes the sequence of an mRNA codon, but not the meaning

Question 14

Describe neutral mutation

Answer 14

Missense mutation that alters the amino acid sequence but does not change the function of the protein

Question 15

What does loss of function mutation cause?

Answer 15

The complete or partial absence of a normal protein function - usually recessive

Question 16

What does gain of function mutation produce?

Answer 16

An entirely new trait or causes it to appear in an inappropriate tissue or at an inappropriate time

Question 17

We generally think of mutations affecting the coding sequence, but they often impact what?

Answer 17

The promotor, 5’ or 3’ noncoding sequences, splice junctions, enhancers

Question 18

Describe suppressor mutation

Answer 18

Genetic change that hides or suppresses the effect of another mutation
Two types:
Intragenic and intergenic

Question 19

Describe intragenic

Answer 19

Suppressor mutation that occurs in same gene as that containing the mutation being suppressed. Results of the second mutation restores a wild-type phenotype.
Second mutation at a different site in the SAME gene.

Question 20

Describe intergenic

Answer 20

Suppressor mutation that occurs in gene other than the one bearing the original mutation

Question 21

DNA pairing is not always perfect, when mispairing due to altered protonation happens what results?

Answer 21

An altered nucleotide that does not get corrected in the next round of replication

Question 22

Which type of base substitution is usually more common?

Answer 22

Transition mutations
Although transversions would seem to be statistically favored because there are eight possible transversions and only four possible transitions, about twice as many transition mutations are actually observed in the human genome

Question 23

Briefly describe expanding nucleotide repeats

Answer 23

Expanding nucleotide repeats occur when DNA insertion mutations result in an increase in the number of copies of nucleotide repeat sequence. May account for the penomenon of anticipation.

Question 24

How can expanding nucleotide repeats occur?

Answer 24

Such an increase in the number of copies of a nucleotide sequence may occur by errors in replication or unequal recombination.

Question 25

Describe anticipation

Answer 25

Within a given family, a particular type of nucleotide repeat may increase in number from generation to subseqent generation, increasing the severity of the mutation

Question 26

What are the types of intragenic suppression?

Answer 26

1. Restores the original phenotype by reverting the meaning of a previously mutated codon to that of the original codon. Occurs at a different position than the first mutation.
2. May also occur at two different locations within the same protein. If two regions of a protein interact, a mutation in one of these regions could disrupt that interaction. The suppressor mutation in the other region would restore the interaction
3. Frameshift mutation could be suppressed by a second insertion or deletion that restores proper reading frame

Question 27

How do insertion and deletions arise?

Answer 27

Strand slippage that occurs during DNA replication

Unequal crossover events due to misalignment at repetitive sequences

Question 28

What does strand slippage result from?

Answer 28

Results from the formation of small loops on either the template or the newly synthesized strand. If the loop forms on template strand = deletion
If the loop formes on newly synthesized strand = insertions

Question 29

If, during crossing over, a misalignment of the two strands at repetitive sequence occurs, then the resolution of the crossover will result in what?

Answer 29

One DNA molecule containing an insertion and the other molecule containing a deletion

Question 30

How do base analogs lead to mutations?

Answer 30

Base analogs have structures similar to the normal nucleotides and if present, they may be incorporated into the DNA during replication
Many have an increased tendency for mispairing, which can lead to mutations.
Needs DNA replication to be incroporated

Question 31

What is loss-of function mutation?

Answer 31

Causes a complete or partial loss of function

Question 32

What is Gain-of-function mutation?

Answer 32

Causes the appearance of a new trait or function or causes the appearance of a trait in inappropriate tissue or at an inappropriate time

Question 33

What is lethal mutation?

Answer 33

Causes premature death

Question 34

What are the five spontaneous replication errors?

Answer 34

Tautomeric shifts
Mispairing due to other structures
Incorporation errors and replication errors 
Strand slippage
Unequal crossing over

Question 35

What is depurination?

Answer 35

loss of purine

Question 36

What is deamination?

Answer 36

loss of an amino group

Question 37

How do alkylating agents produce mutations?

Answer 37

Alkylating agents donate alkyl groups (either methyl or ethyl) to the nucleotide bases. This addition results in misspairing of the alkylated base and typically leads to transition mutations

Question 38

How does nitrous acid produce mutations?

Answer 38

Mutagen that results in the deamination of cytosine, producing uracil, which pairs with adenine
During the next round of replication, A CG to AT transition will occur
Deamination of guanine by nitrous acid produces xanthine. Xanthine can pair with either cytosine or thymine . CG to TA

Question 39

How does hydroxylamine cause mutations?

Answer 39

Works by adding a hydroxyl group to cytosine, producing hydroxylaminocytosine.
This has an increased tendency to undergo tautomeric shifts, which allow pairings with adenine, resulting in GC to AT transition

Question 40

Base analogs are mutagenic because of which characteristics?

a. They produce changes in DNA polymerase that cause it to malfunction
b. They distort the structure of DNA
c. They are similar in structure to the normal bases
d. They chimically modify the normal bases

Answer 40

C

Question 41

What mutation can radiation cause?

Answer 41

Pyrimidine dimers, where two thymines bind and they thus block replication

Question 42

What is the purpose of the Ames test?

Answer 42

Ames test allows for rapid and inexpensive detection of mutagenic and potentially carcinogenic compounds using bacteria. The majority of carcinogenic compounds results in DNA damage and are mutagens

Question 43

How are his- bacteria used in the Ames test?

Answer 43

The increase reversion rate of his- bacteria to his is used to detect the mutagenic potential of the compound being tested.

Question 44

Mismatch repair in bacteria distinguishes between old and new strands of the DNA on the basis of ______.

Answer 44

Methyl groups on the old strand

Question 45

Describe mismatch repair

Answer 45

Replication errors that are the result of base-pair mismatches are repaired. The enzymes recognize distortions in the DNA structure due to mispairing and detect the newly synthesized strand by the lack of methylation on the new strand. the bulge is excised and DNA polymerase fills the gap and DNA ligase seals the repair

Question 46

Describe direct repair

Answer 46

DNA damage is repaired by directly changing the damaged nucleotide back to its original structure. Repair done by photolyase or methyltransferase for example

Question 47

Describe base-excision repair.

Answer 47

After the damaged base is removed by glycosylases, the phosphodiester bond is excised by AP endonucleases and other enzymes remove the deoxyribose sugar; then the entire nucleotide is replaced by DNA polymerase and the nick is sealed by DNA ligase

Question 48

What are the two major mechanisms for repair of double-strand breaks?

Answer 48

Homologous recombination and nonhomologous end joining

Question 49

What does homologous recombination require?

Answer 49

An identical DNA molecule (usually a sister chromatid) to repair a double-strand break.

Question 50

What does nonhomologous end joining not require?

Answer 50

A template