Gene Mutation, DNA repair, and Homologous Recombination Flashcards
what provides the raw material for evolution
genetic variation among individuals
DNA sequence polymorphism vs. mutations
Mutations: rare(<1% in pop), causes disease or disorder
Polymorphisms: more common(>1% in pop), usually neutral
4 different mutation categories and what they’re caused by
Spontaneous: happen naturally and randomly
Induced: Result from extraneous factor
Somatic: don’t occur in germ cells and are not heritable
Germ-line: occur in gametes(heritable)
what is a point mutation
a change of one base pair into another in a DNA molecule
missense mutation
base pair change that results in an AA change in the protein
silent(synonymous mutation)
point mutation that does not alter the AA chain
nonsense mutation
a base pair change that creates a stop codon rather than an AA codon
what are the two base pair mutations
Transition: purine replaces purine, or pyrimidine replaces pyrimidine
Transversion: pyrimidine replaces purine and vice versa
types of frameshift mutations and their consequences
insertion or deletion
-possibly cause
*premature stop codon
*nonsensical AA sequence
*excessively long
point mutations vs frameshift mutations
point: replaces one base with another
Frameshift: shortens or lengthens AA chain
3 regulatory mutations
promoter
Splicing
Cryptic splicing
promoter mutation
alter promoter sequences which interferes with transcription initiation
splicing mutation
prevent efficient splicing of introns
Cryptic splicing
base-pair substitution that produce new splice sites
2 types of functional effects on alleles
loss of function
gain of function
examples of loss and gain of function mutations
Loss: Tay-Sachs and double muscling
Gain: Huntingtons and Philadelphia chromosome
what is a neutral mutation
mutation in non coding regions
what causes slippage
DNA polymerase temporarily disassociates and a portion of newly replicated DNA forms a temporary hairpin
what do trinucleotide repeat expansion disorders come from?
how does it correlate to threshold repeat ranges?
arise from strand slippage
if repeats increase beyond threshold it causes the disorder
incorporated vs replicated errors
Incorporated: G-T or A-C pairing
Replicated: replication of the incorporated error(initial A-T becomes C-G after replication)
depurination vs deamination
Depurination: loss of purine through breaking covalent bond to sugar
Deamination: loss of amino group from a nucleotide base
what is an apurinic site
site caused by depurination
how can DNA polymerase compensate for an apurinic site
placing an adenine into the site during replication
what is the most common cause of spontaneous mutations
base damage from depurination or deamination
what is a mutagen
natural or artificial agents that induce mutations
mutagen modes of action
nucleotide base analogs
deaminating agents
alkylating agents
oxidizing agents
hydroxylating agents
intercalating agents
what chemical mutagen is common for genetic screens
EMS
what is DNA nicking caused by?
what can it lead to if not repaired?
distortion of DNA from intercalating agents
can cause frameshift mutations
T/F nucleotides can be added or lost from DNA nicking
TRUE
what is a photoproduct
aberrant structures with additional bonds involving nucleotides due to UV irradiation
2 common photoproducts
Thymine dimer: covalent bond between 5 and 6 carbons of adjacent thymines
6-4 photoproduct: covalent bond between carbon 6 of one thymine and carbon 4 of another
T/F disruption of replication is the primary cause for the strong association between UV exposure and skin cancer
TRUE
differences in what gene leads to diversity in dog sizes
IGF1
a missense mutation in what gene leads to the size of Shetland ponies
aggrecan gene
what gene and type of mutation causes hairless dogs
7-basepair duplication within exon 1 produces a stop codon(nonsense mutation)
main principles of proofreading-mismatch repair
Proofreading: immediately after replication to find mistakes
Mismatch: after proofreading, cuts out mistake and replaces it with correct base
principles of excision repair
-endonucleases: cut error from strand
-DNA polymerase: fills gap with nucleotides
-DNA ligase: seals gap at 3’ OH end
T/F photoactivation repair occurs in humans
FALS
how does base excision repair occur?
what is the role of nick translation?
repair or replace a damaged or incorrect base
-DNA glycosylases recognize and remove base creating an AP site which creates a single stranded nick
-DNA polymerase removes area around nick which is filled in by nick translation
what genes are involved in NER
uvrA, uvrB, uvrC, and uvrD
how does sister chromatid exchange occur?
can it lead to mutations?
repair of double-stranded breaks
yes it can cause mutations
what mechanisms/processes fix out DSBs
NHEJ
homologous recombination repair
when do DSBs occur
S phase of mitosis
what causes bloom’s syndrome
mutation in DNA helicase BLM gene
what plant was used to study SCE?
what mutagens were used to create the SCE?
Barley
Maleic acid hydrazide(MH) was used
what kind of gain of function mutation was EOE?
what gene was it on?
neomorphic
stat1
what are regulatory mutations
mutations that affect regions such as promoters, introns, and coding for 5’ and 3’ UTR segments
steps of NHEJ
-Ku80 protein complex binds DNA ends
-ends are trimmed causing loss of nucleotides
-DNA ligase ligates blunt ends to reform an intact duplex
steps of homologous recombination repair
-nucleases digest a portion of broken strands, Rad51 binds undamaged chromatid
-replication fork assembles on D loop of sister chromatid
-new strand synthesis occurs using intact sister strand as template
-partial strand excision occurs, duplexes reform, strands are ligated
