Ch 18 Gene Mutations & DNA Repair Flashcards
a heritable change in the DNA sequence of genetic information
mutation
mutations that arise in somatic cells, which don’t produce gametes
mutation is passed on to all daughter cell, leading to clones
somatic mutations
mutations that arise in germ-line cells, which produce gametes and can be passed on to future generations
germ-line mutations
mutations that affect a single gene or locus
only detected by observing phenotypic effects
gene mutations
mutations that affect number or structure of chromosomes
can be deserved directly
chromosome mutations
alteration of a single nucleotide in the DNA
base substitution
what is a transition base substitution?
a purine is replaced by a different purine; a pyrimidine is replaced by a different pyrimidine
what is a transversion base substitution?
a purine is replaced by a pyrimidine; a pyrimidine is replaced by a different purine
what is a transversion base substitution?
a purine is replaced by a pyrimidine; a pyrimidine is replaced by a different purine
which arise more frequently? transitions or transversions? why?
transitions; easier to transform a base into its same type rather than a different one
one or more nucleotides added into DNA sequence
insertion
one or more nucleotides removed from DNA sequence
deletion
mutations that result in changes in the reading frame of a gene
frame-shift mutations
why do frameshift mutations generally have drastic effects on the phenotype?
frameshift mutations usually alter all amino acids encoded by the nucleotides following the mutation
insertions/deletions that do not change the reading frame
in-frame insertions / in-frame deletions
how do in-frame insertions/in-frame deletions arise?
insertions and deletions in multiples of 3 nucleotides leave the reading frame intact
mutations where the number of copies of a set of trinucleotides increases
expanding trinucleotides repeats
explain how expanding nucleotide repeats leads to anticipation
the more copies of the repeat present, the more likely the repeats will increase, and diseases caused by these expanding repeats become more severe in each generation
what trinucleotide sequence is most often present in most diseases caused by expanding trinucleotide repeats
CNG
explain how strand slippage can cause expansion of nucleotide repeats
During replication, DNA strands separate and begin replication. During replication, a hairpin may form on the newly synthesized strand, causing the sequence to be replicated twice, increasing the number of repeats on the new strand. In another round of replication of the new strand, the new DNA molecule contains addition copies of the repeated nucleotides
mutation that alters the wild-type phenotype
forward mutation
mutation that changes mutant back to wild-type phenotype
reverse mutation
mutation that results in a different amino acid in the protein
missense mutation
mutation that changes a sense codon into a stop codon, terminating translation
nonsense mutation
mutation that doesn’t change the amino acid sequence
silent mutation
missense mutation that alters the amino acid sequence of a protein but does not change its function
neutral mutation
mutation that causes the complete or partial absence of normal protein function
loss-of-function mutation
mutation that causes the cell to produce protein or gene product with a new function
gain-of-function mutation
mutations expressed only under certain conditions
conditional mutations
mutations that cause premature death
lethal mutations
mutation that hides the effect of another mutation at a nucleotide distinct from the original mutation site
suppressor mutation
explain how suppressor mutations are different than reverse mutations
suppressor mutations occur at a site different from the site of the original mutation, whereas a reverse mutation changes the mutated site back back to its original wild-type
suppressor mutation that takes place within the same gene that contains the mutation being suppressed
intragenic suppressor mutation
explain how intragenic suppressor mutations occur (three ways)
-suppressor may change a second nucleotide at a different site in the same gene to restore the original amino acid
-suppressor may suppress a frameshift mutations, by inserting or deleting a nucleotide
-making compensatory changes in the protein
suppressor mutation that occurs in a gene different than the one with the original mutation that it suppresses
intergenic suppressor mutation
explain how an intergenic suppressor mutation can occur
a second mutation that encodes for a tRNA that is capable of pairing with the original mutation’s codon
the frequency with which a wild-type allele changes to a mutant allele
mutation rate
list the three factors that affect mutation rates
- frequency that a mutation takes place
- probability a mutation is repaired
- probability mutation is detected
mutations that arise from natural changes in DNA or replication errors
spontaneous mutations
mutations that are caused by environmental agents, like chemicals or radiation
induced mutations
explain how strand slippage causes a deletion
template strand of DNA loops out, resulting in a nucleotide being omitted on the newly synthesized strand
explain how strand slippage causes an insertion
the newly synthesized strand loops out, resulting in an extra nucleotide being synthesized in the next round of replication
explain how unequal crossing over causes insertions and deletions
when homologous chromosomes misalign, they crossover, and one chromosome has an insertion where the other has a deletion
the loss of a purine base from a nucleotide
depurination
how does depurination occur? what is produced?
the covalent bond connecting a purine to the 1’ carbon atom of deoxyribose breaks, producing an apurinic site
a nucleotide that lacks its purine base
apurinic site
what results from the presence of an apurinic site
since the apurinic site cannot act as a template for a complementary base during replication, an incorrect nucleotide (usually adenine) is incorporated in the new DNA strand
a base substitution causes a mispaired base to be incorporated into a newly synthesized nucleotide chain
incorporated error
the loss of an amino group from a base
deamination
what results from deamination?
deamination can alter the pairing properties of a base, causing it to pair with a different nucleotide than it’s supposed to
what occurs from the deamination of cytosine?
cytosine is turned into uracil, which then pairs with adenine
instead of a CG pair, a UA pair forms, which replicates into T*A
any environmental agent that significantly increases the rate of mutation above the spontaneous rate
mutagen
chemicals with structures similar to those of any of the four standard nitrogenous bases of DNA and can be incorporated into new DNA
base analogs
explain how base analogs can cause mutations
base analogs can be incorporated into new DNA, instead of the standard base. the base analog may pair with the original complementary base, but it may also pair with a different base, causing a mutation
molecules similar to the size of nucleotides that can sandwich themselves between adjacent bases in DNA
intercalating agents
what are the effects of intercalating agents?
by intercalating between bases in DNA, the 3D DNA helix is distorted, causing insertions and deletions, thus producing frameshift mutations
what are the effects of ionizing radiation from X-rays, gamma rays, cosmic rays, etc
they dislodge electrons from atoms, changing them into free radicals and reactive ions, which then alter structures of bases and break phosphodiester bonds, and frequently cause double-strand breaks in DNA
what is the effect if UV light
UV light has less energy, and pyrimidines absorb UV light, resulting in the creation of pyrimidine dimers
how do pyrimidine dimers form?
pyrimidines absorb UV light, causing chemical bond to form between two adjacent pyrimidines on the same DNA strand, which distorts the normal DNA configuration, often blocking replication
DNA sequences that are capable of moving around in the genome
transposable elements (transposons_
how can transposable elements cause mutations?
transposons insert themselves into a gene and disrupt it; or promote chromosome rearrangements
what are the general characteristics of transposable elements (two of them)
short flanking direct repeats
terminal inverted repeats
what are flanking direct repeats? how are they associated with transposons? how do they arise?
flanking direct repeats are short, directly repeated sequences (~3-12 bp) present on both sides of the transposon
they are not a part of the transposon
staggered cuts made in target DNA produced short single-stranded pieces of DNA on either side of transposon. replication of these ends produces the flanking direct repeats
what are terminal inverted repeats and how are they associated with transposons?
terminal inverted repeats are sequences at both ends of a transposon that are inverted complements of one another
why are terminal inverted repeats required for transposition?
enzymes catalyzing transposition recognize these sequences in order to locate the transposon
movement of a transposable element from one location to another
transposition
what are the three steps of transposition?
- staggered breaks made in target DNA
- transposable element joined to single-stranded ends of target DNA
- DNA is replicated at single-stranded gaps
enzyme that makes single-stranded breaks in DNA during transposition, and is often encoded by the transposon
transposase
transposable elements that transpose as DNA
DNA transposons
transposable elements that transpose through an RNA intermediate
retrotransposons
how does a retrotransposon move?
a transposable element (DNA) is transcribed into RNA, which is then copied back into DNA by reverse transcriptase
new copy of transposable element moves to a new site while the original transposable element remains at its old site, therefore increasing the number of transposon copies
replicative transposition
transposable element is excised from its original site and inserted into a new site, therefore no increase in transposon copies
nonreplicative transposition
describe mismatch pair
incorrectly paired bases and small unpaired loops in DNA are detected and corrected by mismatch-repair enzymes
mismatch-repair enzymes used original DNA strand as template to correct the error
how do mismatch-repair enzymes distinguish between the old and new strands of DNA (in bacteria)
old strands contain methyl groups (on the adenine nucleotides)
describe direct repair
modified bases are restored back into their original (correct) structures
describe base-excision repair
a modified base is excised, then the entire nucleotide is replaced
describe nucleotide-excision repair
bulky lesions that distort the DNA double helix are removed, and any other DNA damage
