chapter 11 part 1 Flashcards
germ-line mutations
mutations that occur in germ-line cells (give rise to sperm/egg)
how are germ-line mutations passed on
from one generation to the next
somatic mutations
mutations in cells not in the germ line
how are somatic mutations passed on
somatic cells divides by mitosis, only direct descendants carry mutation
what do gene mutations do to DNA base pairs
substitute, add, or delete one or more DNA base pairs
point mutations
localized mutations that occur at specific, identifiable position in a gene
mutation hotspots
genes with elevated mutation rates
characteristics of mutation hotspots
- large gene size
- regions rich in CpG dinucleotides
- long stretches of trinucleotide repeats
ex. of mutation hotspots
- DYS gene (Duchenne muscular dystrophy)
- NF1 gene (nuerofibromatosis)
base-pair substitution mutations
replacing one nucleotide with another
transversions
base-pair substitution going from purine to purine or pyrimidine to pyrimidine
transitions
base-pair substitution going from pyrimidine to purine or reverse
3 types of base-pair substitutions
- silent (synonymous)
- missense
- nonsense
silent (synonymous) mutation
no amino acid change
missense mutation
change in amino acid
nonsense mutation
creates stop codon
frameshift mutations
insertion or deletion of one or more base pairs altering reading from of the message
what are frameshift mutations also called
INDEL
- insertion or deletion
what is produced as a result of frameshift mutations
the wrong amino acid sequence and sometimes premature stop codons
promoter mutation
mutations that alter consensus sequence nucleotides of promoters
what do promoter mutations interfere with
efficient transcription initiation
what does efficient splicing of introns from mRNA require
specific sequences at either end of the intron
splicing mutation
mutation that results in splicing errors and production of mutant proteins due to retention of intron sequences in the mRNA
cryptic splice sites
when some base-pair substitutions produce new splice sites that replace/compete with authentic splice sites during mRNA processing
polyadenylation mutations
mutation in polyadenylation signal sequence at 3’ end of euk. mRNA that can block 3’ processing
ex. of polyadenylation mutation
human B-globin gene
- coding strand is mutated
- Beverly reduces amount of functional protein produced
forward mutation
converse wild-type allele to a mutant allele
reverse mutations (reversions)
convert mutant alleles to wild-type or near wild-type
true reversion
wild-type DNA sequence or amino acid sequence is restored by a second mutation within the same codon
intragenic reversion
occurs through mutation elsewhere in same gene
second-site reversion
occurs by mutation in different gene and together the 2 mutations restore the organism to wild-type
what are second-site reversions also know as
suppressor mutations
- second mutation suppresses mutant phenotype caused by first mutation
spontaneous mutations
arise in cells without exposure to agents capable of inducing mutation (mutagens)
how do spontaneous mutations arise
- errors in DNA replication
- spontaneous changes in the chemical structure of a nucleotide base
why did DNA replication have high fidelity
due to accuracy of DNA polymerases, proofreading ability of DNA pol, and efficiency of mismatch repair
mismatches due to replication errors occur at rate of about ____________ in wild-type E. coli and same in euk.
1 x 10^-9
how do alterations in number of DNA repeats occur
strand slippage
strand slippage process
- DNA polymerase of replisome temporarily dissociates from template
- portion of newly replicated DNA forms a temporary hairpin
- resumption of replication leads to re-replication of some of the repeats and overall increase in number of repeats on daughter strand
trinucleotide repeat disorders
special class of mutations causing some hereditary diseases in humans and other organisms
- increases number of characteristic trinucleotide repeats beyond certain threshold
depurination
loss of a purine from a nucleotide by breaking the covalent bond linking the nucleotide base to the sugar
apurinic site
lesion where deprivation occurs
when are most AP sites repaired
before replication
what happens when AP sites are left unrepaired
DNA pol will usually compensate by putting an adenine into the site during replication
deamination
loss of amino group from a nucleotide
what happens when cytosine is deaminated
an oxygen atom usually takes its place, converting the cytosine into uracil
- DNA mismatch repair removed uracil from DNA and replaces it with cytosine to restore wild-type sequence
what happens when methylated cytosine is deaminated
- thymine base is produced
- then base-pairs with guanine
- mismatch repair system can restore wild-type G-C pair
- if repair doesn’t occur, replication will produce 2 sister chromatids, one w/ mutant A/T pair and one with wild G/C pair
induced mutations
produced by mutagens in an experimental setting to study types of damage caused, the mutation process itself, or repair responses to damage
mutagens
agents that cause DNA damage leading to mutations
chemical mutagens can be classified by their modes of action on DNA as:
- nucleotide base analogs
- deaminating agents
- alkylating agents
- oxidizing agents
- hydroxylating agents
- intercalating agents
DNA intercalating agents
distort DNA duplex by fitting between DNA base pairs
- some form bulky adducts that contribute to distortion
what does distortion from intercalating agents lead to
DNA nicking that is not efficiently repaired, resulting in added or lost nucleotides
good DNA stains
- ethidium bromide
- acridine orange
photoproducts
aberrant structures with additional bonds involving nucleotides caused by UV irradiation
pyrimidine dimers
produced by formation of one or two additional covalent bonds between adjacent pyrimidine nucleotides
ex. of 2 common photoproducts
- thymine dimer
- 6-4 photoproduct
thymine dimer
common photoproduct that is formed between the 5 and 6 carbons of adjacent thymines
6-4 photoproduct
formed by bond between carbon 6 on one thymine and carbon 4 on other
types of radiation
X-rays, gamma rays, radioactive materials
most serious damage caused by radiation
single-stranded or double-stranded breaks in DNA
what can breaks in DNA block
replication
- health by with specialized repair systems
organisms preserver the fidelity of DNA using
multiple repair systems
what do multiple repair systems do
- directly repair DNA damage
- allow organism to circumvent the problems caused by unrepaired damage
ex. of direct repair
- proofreading
- photo reactive repair
proofreading activity of DNA polymerase leads to what kind of exonuclease activity?
3 to 5
how can pyrimidine dimers be directly repaired
photo reactive repair
can photo reactive repair take place in humans?
no
photo reactive repair process
- enzyme photolyase uses energy from visible light to break bonds between pyrimidine dimers
- photolyase is encoded by E. coli phr (photo reactive repair) gene
how is DNA damage by alkylating agents repaired
enzymes that remove the added chemical groups, restoring the nucleotide to its normal form
what is direct repair of damage by alkylating agents performed by
class of enzymes called alkyltransferases
alkyltransferases
- remove alkyl groups (methyl/ethyl)
- can reverse effects of EMS and NG
ex. of direct repair of damage by alkylating agents
- O6-methylguanine is converted by to guanine by enzyme O6-methylguanine methyltransferase
- enzyme permanently inactivated after one such reaction
nucleotide base excision repair
multistep process that may repair damage to a nitrogenous base or replace an incorrect base
DNA glycosylases
series of enzymes that recognize specifically modified or incorrect bases and remove modified purine bases, leaving an AP site
base excision repair process
- DNA glycosylases work and create AP site
- AP endonuclease creates single-stranded nick near the AP site
- nick translation: DNA pol initiate removal/replacement of nucleotides, including AP site
- DNA ligase seals the sugar-phosphate backbone
basic nucleotide excision repair process
- enzymes recognize and bind to damaged region
- segment of nucleotides is removed from the damaged strand
- DNA pol fills in the gap and DNA ligase seals sugar-phosphate backbone
what is nucleotide excision repair often used to repair
UV-induced damage to DNA
what is nucleotide excision repair also known as
ultraviolet repair
