Mutations and DNA Damage

Question 1

Transitions Point Mutation

Answer 1

change a purine (A/G) to a different purine (G/A) OR a pyrimidine (T/C) to a different pyrimidine (C/T)

Question 2

Transversions Point Mutation

Answer 2

change a purine to a pyrimidine or vice versa

Question 3

Missense Point Mutation (protein coding gene)

Answer 3

mutation changes a codon so that it causes a different amino acid to be incorporated into the encoded polypeptide chain

Question 4

Nonsense Point Mutation (protein coding gene)

Answer 4

changes an amino acid-encoding codon to a stop codon

Question 5

Silent Point Mutation (protein coding gene)

Answer 5

change the base in the DNA and RNA, but do not affect the amino acid

Question 6

Neutral Point Mutation

Answer 6

occur in noncoding regions of DNA & do not affect gene products or gene expression

Question 7

Point Mutation

Answer 7

Substitution

Question 8

Frameshift Mutation

Answer 8

Deletion or Insertion of a number of bases

Question 9

Frameshift mutaitons alter

Answer 9

Multiple codons

Question 10

Point mutations alter

Answer 10

One codon

Question 11

Loss of Function Mutation

Answer 11

reduce the mutated gene’s function - usually recessive to the wild-type allele

Question 12

Null Mutation

Answer 12

occurs when the mutation causes total loss of the gene product

Question 13

Haploinsufficiency

Answer 13

when one wild-type allele is not enough to produce the wild-type phenotype
because ½ of the protein is not sufficient to do the job

Question 14

Dominant-Negative Mutations

Answer 14

cause the mutant allele to produce a mutated protein
- even if the wild-type allele still makes normal protein, the mutated protein negates (cancels out) the function of the wild-type protein
- therefore, the mutation produces the mutant phenotype even if the wild-type gene copy is still intact

Question 15

Gain of Function Mutation

Answer 15

Increases gene function (usually dominant)

Question 16

Gain of Function mutations may create a structural change

Answer 16

-the Ras gene encodes a key signaling protein that regulates whether cells grow, migrate, and die
-cancer cells frequently mutate Ras in such a way that the protein cannot be turned off

Question 17

Somatic Mutations

Answer 17

are those that occur in any body cell other than germ cells
-are not transmitted to offspring
-have greater impact if they are …
*dominant
*occur on the X chromosome in males
*occur earlier in development

Question 18

Germ Line Mutations

Answer 18

take place in germ cells
-only type of mutation capable of being transmitted to offspring

Question 19

Spontaneous Mutations (slippage, oxidative damage, tautomeric shifts)

Answer 19

-changes in the nucleotide sequence of genes that occur naturally
-no specific agents are associated with their occurrence (unlike induced mutation)
-arise because of normal cellular processes & reactions
*ex – DNA polymerase errors in DNA replication

Question 20

DNA Polymerase Has Intrinsic Proofreading Ability

Answer 20

-DNA polymerases have intrinsic 3’ to 5’ exonuclease activity
-allows them to correct most replication errors
-DNA polymerase make a mistake once every 100,000 bases
*corrects about 99% of these errors
*equates to an error rate of ~ 10-7
mostly mispairing/point mutations

Question 21

Replication Slippage

Answer 21

-most common when polymerase replicates regions of DNA containing tandemly repeated sequences
-may cause insertions/deletions that lead to frameshift mutations

Question 22

Replication Slippage happens when

Answer 22

-when polymerase slips or stutters as it moves along the DNA
-the lagging strand template loops out and becomes displaced during replication

Question 23

Oxidative Damage

Answer 23

from reactive oxygen species (ROS) generated by normal cellular reactions

Question 24

Reactive Oxygen Species (ROS)

Answer 24

-examples of ROS include:
*superoxide anions (O2-)
*hydroxyl radicals (OH-)
*hydrogen peroxide (H2O2)
-ROS may lead to modification or loss of bases in the DNA, or to single-strand breaks

Question 25

Tautomeric Shifts

Answer 25

change covalent structure of a N base and permit H bonding between non-complementary bases -results in permanent base pair change & mutation

Question 26

How does a tautomeric shift result in a permanent base change?

Answer 26

1. a base in the parental DNA strand undergoes a tautomeric shift 2. during DNA replication, that tautomer participates in non-standard base-pairing (A:C, not A:T) 3. when replicated later on, the strand containing “C” at that position recruits a “G”, not the original “A” the base at this position is now permanently changed in this cell & all its descendants

Question 27

Ionizing Radiation

Answer 27

-ionizes stable molecules and atoms, transforming them into highly reactive free radicals with unpaired electrons *alter bases in DNA *break phosphodiester bonds in the DNA backbone *lead to double-strand breaks *cause chromosomal deletions, translocations, and fragmentation -20% of human radiation exposure comes from human-made sources -majority of our exposure comes from radon gas, cosmic rays, and natural soil radioactivity

Question 28

Alkylating Agents

Answer 28

-donate an alkyl group (e.g. CH3 or CH2CH3) to an amino or keto group in a nucleotide *alter bp affinities & lead to transitions -mustard gas from WWI was an alkylating agent that creates a base analog that pairs with thymine

Question 29

Intercalating Agents

Answer 29

-wedge between base pairs of DNA -cause distortion of DNA structure & induce unwinding *leads to insertions/deletions during replication

Question 30

Adduct Forming Agents

Answer 30

-covalently bind DNA & interfere with replication and repair (causing slippage) -examples include acetaldehyde (cigarette smoke) & heterocyclic amines (meats)