Lecture 14 Mutations and Repair Ch. 18 Flashcards
What are the two major categories of mutations?
Somatic and Germ-line
Somatic mutations arise where?
In tissues other than those that produce gametes
What mutations are restricted to the individual?
Somatic mutations
Germ-line mutations arise where?
In tissues that produce gametes
What mutations can be passed to offspring?
Germ-line mutations
What are transition mutations?
Base substitutions: Purine replaced by purine; pyrimidine replaced by pyrimidine
What are transversion mutations?
Base substitutions: Purine replaced by pyrimidine or vice versa
What are the types of frameshift mutations?
Insertions, and deletions
Describe forward mutations
Mutation that alters the wild-type phenotype
Describe reverse mutation
Mutation that changes the mutant phenotype back into the wild-type
Describe missense mutations
Base substitution that changes the sequence and the meaning of a mRNA codon, resulting in a different amino acid being inserted into a protein
Describe nonsense mutation
Mutation that changes a sense codon into a termination codon
Describe silent mutation
Mutation that changes the sequence of an mRNA codon, but not the meaning
Describe neutral mutation
Missense mutation that alters the amino acid sequence but does not change the function of the protein
What does loss of function mutation cause?
The complete or partial absence of a normal protein function - usually recessive
What does gain of function mutation produce?
An entirely new trait or causes it to appear in an inappropriate tissue or at an inappropriate time
We generally think of mutations affecting the coding sequence, but they often impact what?
The promotor, 5’ or 3’ noncoding sequences, splice junctions, enhancers
Describe suppressor mutation
Genetic change that hides or suppresses the effect of another mutation
Two types:
Intragenic and intergenic
Describe intragenic
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.
Describe intergenic
Suppressor mutation that occurs in gene other than the one bearing the original mutation
DNA pairing is not always perfect, when mispairing due to altered protonation happens what results?
An altered nucleotide that does not get corrected in the next round of replication
Which type of base substitution is usually more common?
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
Briefly describe expanding nucleotide repeats
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.
How can expanding nucleotide repeats occur?
Such an increase in the number of copies of a nucleotide sequence may occur by errors in replication or unequal recombination.
Describe anticipation
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
What are the types of intragenic suppression?
- 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.
- 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
- Frameshift mutation could be suppressed by a second insertion or deletion that restores proper reading frame
How do insertion and deletions arise?
Strand slippage that occurs during DNA replication
Unequal crossover events due to misalignment at repetitive sequences
What does strand slippage result from?
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
If, during crossing over, a misalignment of the two strands at repetitive sequence occurs, then the resolution of the crossover will result in what?
One DNA molecule containing an insertion and the other molecule containing a deletion
How do base analogs lead to mutations?
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
What is loss-of function mutation?
Causes a complete or partial loss of function
What is Gain-of-function mutation?
Causes the appearance of a new trait or function or causes the appearance of a trait in inappropriate tissue or at an inappropriate time
What is lethal mutation?
Causes premature death
What are the five spontaneous replication errors?
Tautomeric shifts Mispairing due to other structures Incorporation errors and replication errors Strand slippage Unequal crossing over
What is depurination?
loss of purine
What is deamination?
loss of an amino group
How do alkylating agents produce mutations?
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
How does nitrous acid produce mutations?
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
How does hydroxylamine cause mutations?
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
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
C
What mutation can radiation cause?
Pyrimidine dimers, where two thymines bind and they thus block replication
What is the purpose of the Ames test?
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
How are his- bacteria used in the Ames test?
The increase reversion rate of his- bacteria to his is used to detect the mutagenic potential of the compound being tested.
Mismatch repair in bacteria distinguishes between old and new strands of the DNA on the basis of ______.
Methyl groups on the old strand
Describe mismatch repair
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
Describe direct repair
DNA damage is repaired by directly changing the damaged nucleotide back to its original structure. Repair done by photolyase or methyltransferase for example
Describe base-excision repair.
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
What are the two major mechanisms for repair of double-strand breaks?
Homologous recombination and nonhomologous end joining
What does homologous recombination require?
An identical DNA molecule (usually a sister chromatid) to repair a double-strand break.
What does nonhomologous end joining not require?
A template
