Ch12 | Mutation Flashcards
A mutation only becomes stable and heritable when…
(1) It occurs within germ line (gametic)
(2) Is duplicated
(3) Is base-paired appropriatel
Mutation
Change in DNA sequence
Point mutation
Change in a single base pair
Transition
Purine to Purine or Pyrimidine to Pyrimidine
Transversion
Purine to Pyrimidine or vice-versa
Silent mutation
When the mutation results in coding for same amino acid (synonymous codon)
Missense mutation
Change in codon resulting in different amino acid
Nonsense mutation
Change that no longer codes for amino acid and instead terminates or stops translation
Steps (2) of Point Mutation
(1) DNA Polymerase places incorrect nucleotide
(2) Repair fails to occur and base-pairing occurs
Evolution due to mutation…
(1) Requires selective advantage
(2) Is rare
In drosophila, how often were mutations found to be deleterious?
~70% of the time
Oncogenes
Code for proteins that drive cell division cycle
Tumor suppressor genes
Code for proteins that suppress cell division
Insertion
Addition of one or more codons to wild-type sequence
Deletion
Loss of one or more nucleotides from wild-type sequence
Indels
Category including insertions and deletions
Reading frame
DNA sequence from start codon to stop codon
Frameshift
Change in reading frame due to one or two indels, because codons are read in triplets
What is the typical result of a frameshift mutation?
Truncated protein
Triplet expansion disease
Potential result of insertion of three novel nucleotides (codon triplet)
Polyglutamine (PolyQ) diseases
The majority of triplet expansion diseases, involving CAG insertion, such as Huntington’s chorea
Duplication mutation
Amplification of large tract of DNA leading to increased dosage effect
Inversion mutation
Result of inversion of large tract of DNA sequence
Translocation mutation
Exchange of DNA between non-homologous chromosomes
Fusion gene
When a mutation results in hybridization of two different genes
Why is water a key contributor to mutation?
It is the universal intracellular solvent
Why is DNA vulnerable to alkylation and oxygen-reactive agent?
The high degree of negative charge along its backbone
Deamination
Removal of amino group from molecule or compound
Hydrolytic attack
Primary weakness of any amino group containing complex
Which three (3) nucleotides contain an amino group?
(1) C
(2) A
(3) G
What is the most common deamination in nucleotides and what is the result?
Cytosine deamination results in Uracil (100X more common)
Why is deamination of adenine or guanine different in their outcome when compared to cytosine?
The resulting base pairs are not normally found in nucleotides and are likely to be deleterious
CpG sequence
Methylation of C residue followed by G
Abasic site
Loci missing nucleotide base
Depurination
Hydrolysis of N-B-gylcosyl bond on a purine
Alkylation
Addition of alkyl group to nucleotide
Carcinogen
Any substance directly causing cancer
Genotoxic
DNA-reactive compounds
Cytotoxic
Mutagen with lethal result
Ames test
Standard for mutagen identification
Auxotroph
Organism unable to synthesize all of its own organic compounds necessary for survival
Reversion mutation
Mutation that undoes previous mutation
Pyrimidine dimer
UV induced cross-link binds between a pair of pyrimidines
Mismatch Repair
Repair due to errors in replication process
Dam methylase
Enzyme that provides strand discrimination in bacteria
DNA photolyase
Enzyme of direct repair driven by photo-reactive energy mechanism
Two (2) types of excision repair
(1) Base
(2) Nucleotide
DNA glycosylase
Recognizes point of base excision repair
AP endonuclease
Cleaves abasic site during base repair in preparation for placement of new base
Nucleotide Excision Repair
Removal and replacement of larger, damaged sequence segments along with adjacent DNA
How are DNA lesions likely to be removed and replaced?
Nucleotide excision repair
Transcription-coupled repair
Use of NER by eukaryotes to target stalled RNA polymerase on a damaged nucleotide
Translesion synthesis
Use of a bypass polymerase to overcome obstructive lesion
