BIOL 306 - Chapter Eighteen: Gene Mutations & DNA Repair

Basic Classes of Mutations

Somatic & Germ-Line

Somatic Mutation

Mutation that occurs in nonreproductive cells

Germ-Line Mutation

Mutation that occurs in cells that give rise to gametes

True or False: Somatic mutations are passed to new cells through meiosis

False: Passed through mitosis

Germ-line mutations are passed to the next generation through _____________ and _____________

meiosis; sexual reproduction

Germ-line mutations are passed to approximately ________ of the next generation

half

Categories of Gene Mutation

1. Base substitutions

2. Insertions

3. Deletions

Base Substitution Examples

Transition & Tranversion

Insertion and Deletion Examples

Frameshift mutations, in-frame insertions & deletions

Expanding Nucleotide Repeats

Increase in number of copies of nucleotide set

Transition vs. Transversion

Transition: Substitution of purine for purine or pyrimidine for pyrimidine

Transversion: Substitution of purine for pyrimidine or pyrimidine for purine

Forward Mutation vs. Reverse Mutation

Forward Mutation: Wild type → Mutant type

Reverse Mutation: Mutant type → Wild type

Missense Mutation

Base-pair substitution that converts one amino acid to another amino acid

Nonsense Mutation

Base-pair substitution that converts a sense codon to a nonsense/stop codon

Silent Mutation

Base-pair substitution that changes the codon, but not the amino acid

Neutral Mutation

Base-pair substitution that alters the amino acid sequence but does not alter protein function

Mutations in coding sequences appear in ___________

mRNA

What mutations tend to shift the reading frame?

Insertions and deletions

Where do insertions and deletions tend to take place?

Repeated DNA sequences

When do insertions and deletions tend to take place?

Replication or recombination

True or False: Looping out of nucleotide strand during DNA synthesis can cause extra nucleotides to be synthesized

True

Trinucleotide Repeat Expansion Mutation

Misalignment of repeat amino acid sequence (ex. CAG) that loops out and creates semi-stable DNA hairpin

Trinucleotide repeat expansion mutations are observed in what disease?

Huntington's

Adaptive Mutation

Genetic variation critical for evolutionary change that brings about adaptation to new environments

True or False: Stressful conditions induce increased mutations in bacteria

True

Potential Causes of Mutations

1. Spontaneous replication errors

2. Spontaneous chemical changes

3. Chemically induced mutations

4. Radiation

Slippage

Looping out of newly synthesized strand or template strand

Slippage of the newly synthesized strand causes ____________, while slippage of the template strand causes ____________

insertion; deletion

Tautomeric Shift

Shift in proton position that results in a rare tautomeric form of purines or pyrimidine

The guanine tautomer base-pairs with the common form of ____________, while the cytosine tautomer base-pairs with the common form of ____________

thymine; adenine

Deamination

Removal of amino group

Deamination of cytosine leads to ____________, while deamination of 5-methylcytosine leads to ____________

uracil; thymine

Examples of Chemically Induced Mutations

Mutagen & Base Analogs

True or False: Chemicals may alter DNA bases

True

Causes of Chemically Induced Mutations

Oxidative Reaction & Intercalating Agents

Oxidative Reaction

Superoxide radicals (ex. hydrogen peroxide)

Intercalating Agents

Proflavin, acridine organge, ethidium bromide

Intercalating agents alter the structure of DNA by _______________

inserting themselves into adjacent DNA bases

True or False: Radiation greatly increases mutation rates in all organisms

True

Pyrimidine Dimer

Two thymine bases covalently bonded together that block replication

Pyrimidine dimers result from _________________

ultraviolet light

Ames Test Function

Identifies chemical mutagens; widely used to screen chemicals for cancer-causing potentials

True or False: Mutagenic activity and carcinogenic potential are closely correlated

True

Transposable Element

Sequence that can move about the genome

Transposition

Movement of transposons

Features of Transposable Elements

Flanking direct repeats and terminal inverted repeats

Common Characteristics of Transposable Elements

1. Flanking direct repeats on each side of insertion point into target DNA

2. Possess terminal inverted repeats

True or False: Flanking direct repeats flank terminal inverted repeats

True

Barbara McClintock

Discovered transposable elements

Variegated corn kernels are caused by _______________

mobile genes

DNA Pathways Repair Changes

1. Mismatch repair

2. Direct repair

3. Base-excision repair

4. Nucleotide-excision repair

Mismatch Repair

Corrects mismatched bases and other DNA lesions

Mismatch Repair Function

Enzymes cut out section of newly synthesized DNA and replace it with new nucleotides

Direct Repair

Restores correct structure of altered nucleotides

Base-Excision Repair Steps

1. Glycosylase enzymes recognize and remove specific modified bases, creating AP site

2. AP endonuclease cleaves phosphodiester bond on AP site 5' end and removes entire nucleotide

3. DNA polymerase adds new nucleotides to exposed 3' OH group

4. DNA ligase seals nick in sugar-phosphate backbone

AP Site

Apurinic/Apyrimidinic Site

Nucleotide-Excision Repair

Removes and replaces damaged DNA segments that distort DNA structure

Nucleotide-Excision Repair Steps

1. DNA strands separated

2. DNA section containing distortion removed

3. DNA polymerase fills in gap

4. DNA ligase seals filled-in gap

Primary Differences Between Base-Excision Repair, Mismatch Repair, and Nucleotide-Excision Repair

Detection & Excision

In base-excision and mismatch repair, nicks are made on _____________ of the DNA, while nicks are made on _____________ of the DNA in nucleotide-excision repair

one side; both sides

Old nucleotides are displaced by DNA polymerase in __________ repair, degraded in __________, and displaced by helicase enzymes in __________

base-excision; mismatch; nucleotide-excision

Base-excision repair, mismatch repair, and nucleotide-excision repair all use _____________ and _____________ to fill in the gap produced by the excision and removal of damaged nucleotides

DNA polymerase; DNA ligase

Xeroderma pigmentosum results from _______________

defects in DNA repair