Theme 4: DNA Replication and Mitosis - Module 4: DNA Mutations Flashcards
understanding the process of gene expression enables us to further appreciate what?
how changes in the genetic information of a cell can affect protein structure and function
what can these changes in genetic information create?
devastating cellular consequences or beneficial adaptation
what are mutations responsible for?
the large array of genes and thus the genetic differences that can be found among different organisms
what are mutations considered the source of?
genetic variation
how can mutations be created?
- due to environmental facts
- arising due to spontaneous mutations
- errors during DNA replication
what do errors in DNA replication lead to? can this be corrected?
- changes at the nucleotide level
- can be corrected - but at times are not corrected
what happens if the error is not corrected?
incorrect nucleotide bases can be used as a template in the next round of replication
what does this result in?
the propagation of the mutation
what are the most common mutations to occur?
these spontaneous mutations
how do the spontaneous mutations occur?
randomly by chance without any cause
is a mutation common or rare for any given nucleotide?
rare
is there variability as to the likelihood that a new mutation will occur at a given nucleotide base pair in a single round of replication across different organisms?
yes
most multicellular animals have a low probability of incurring a new mutation at a particular nucleotide pair in a given round of DNA replication, however what tends to have a higher mutation rate?
viruses
which virus has the most probity out of all viruses?
RNA viruses
what is this due to?
the delicate nature of the RNA backbone of RNA viruses and retroviruses (being more prone to damage and breakage)
what is another reason?
no proofreading capability in RNA genomes
genetic information can be mutated in which cells?
somatic or germline cells
if a mutation occurs in the somatic cell of an individual what will that cell be?
progenitor of a population of identical daughter cells following cell division
what will the division of a cell with a new mutation lead to?
a patch or region of cells with this new mutation
what leads to a larger spread of the mutated somatic cell throughout the body of an organism?
the earlier the developmental cascade of the mutation in a somatic cell
when can the effect of a mutation be largely negligible?
if the mutation arises in a cell that is no longer dividing or is post-mitotic in the G0 cycle
can somatic cell mutations be inherited?
no
what mutations can be passed on to offspring?
germline mutations
why is this?
germ cells are the cells that come together to produce new offspring in sexually reproducing organisms
what does this mean?
every cell in the developing embryo will carry the mutation
what did the experiment by Joshua and Esther Lederberg show?
that mutations such as those of antibiotic resistance in bacteria are random and not directed
what did this experimental setup require allowing?
bacteria to grow into colonies in a petri dish with non-selective supplemented nutrients (agar)
why is one of the plates referred to as non-selective?
since bacterial cells are able to grow and form colonies on it
what happened once bacterial colonies had grown on the non-selective plate?
Lederbergs “stamped” the original plate 1 onto a cloth, and then stamped this cloth onto a new selective plate containing the antibiotic penicillin in the agar
what would this plate only all the growth of?
bacteria that are resistant to penicillin
what is the stamping process refereed to as? what does it preserve?
- replica plating
- the relative arrangement of colonies on the new plate relative to the first agar plate
over time what appeared?
only a few colonies from plate 1 survived the exposure to the penicillin on plate 2 - most other bacteria colonies were killed
what did the Lederbergs predict?
these few colonies must carry a mutation that makes them resistant to the antibiotic penicillin
what does the process of replica plating mean?
the original colony that grew on the penicillin agar could be isolated from the original non-selective agar and used to test the hypothesis
what did the Lederbergs do?
exposed the suspected mutant colony from the original plate 1 to penicillin
how did they do this?
isolated bacteria from the original colony and cultured these cells in medium containing penicillin
what did they get in the end?
a pure culture of antibiotic-resistant bacteria
what is it important to remember?
colonies on plate 1 have never been originally exposed to penicillin
what can be concluded?
the mutation that confers penicillin-resistance excited in the population prior to the bacteria being exposed to penicillin in the experiment
what does this provide evidence for?
that mutations create random genetic variation that may include the beneficial changes such as antibiotic resistance
did the new environment create the beneficial environment?
no
was the random mutation beneficial in the new environment?
yes
how often do spontaneous and induced mutations occur?
frequently
how could this be a problem?
if the cell had not evolved some refined mechanism to repair detectable mutations
if the mutations are left uncorrected what can it lead to?
- cell death
- cancer
- aging
- disease
how else can DNA accrue mutations other than during DNA replication?
due to mutagens or agents that can increase the probability of mutations at specific regions along the DNA
what can a mutagen include?
radiation or chemicals
how can most DNA damage be corrected?
by specialized repair enzymes of the cell
what can DNA ligase do?
repair damages in the DNA backbone
most cells contain DNA ligase that are involved with what?
DNA replication and others that specialize in DNA repair of single stranded breaks
how can mismatching of single nucleotide pairs during DNA replication be corrected?
by the proofreading capabilities of DNA polymerase
what does another proofreading mechanism allow?
scanning of the DNA for potential mismatches as a second level quality control in DNA
what does a mismatched nucleotide pair create?
a kink in the DNA molecule
what is this kink recognized by?
proteins that scan the DNA for damage and errors
what does the identification of a mismatch in the nucleotide sequence lead to?
the single stranded cleavage of the mismatched DNA backbone
how is this done?
by an enzyme some distance away from the mismatched nucleotide region
what is the enzyme usually?
a DNA cutting enzyme called a nuclease
what happens once the correcting nuclease enzyme cuts the backbone?
another enzyme is able to remove successive nucleotides from the cut DNA strand, including the mismatched nucleotide
what other enzymes are then present?
DNA polymerase and DNA ligase
what are these enzymes able to do?
able to induce DNA synthesis to close the gap
what does this create?
an intact DNA strand that matches with accurate complementarity to the template DNA strand
what does this allow?
mismatch repair to be completed
what is a more specialized type of repair mechanism?
base excision
in this mechanism, it is the incorporation of what in DNA that signals that there is a need for DNA repair?
incorporation of a Uracil
what is Uracil and where is it present?
- is a characteristic nucleotide
- present in RNA molecules
what happens if a DNA molecule accidentally incorporates a Uracil into their elongating strands?
the actual presence of Uracil is a signal that is detached by a DNA Uracil gylcosylase enzyme which will cleave the uracil from the sugar DNA backbone itself
what is left behind?
a bare deoxyribose sugar with no attached nitrogenous base
what enzyme detects the lack of a nitrogenous base?
enzyme called AP endonuclease
what does this enzyme do?
cleaves the backbone on either side of the area that lacks a base
what is left?
an open gap
what does this gap require?
addition of a completely new nucleotide
what can now occur at the gap site?
DNA synthesis
what enzymes facilitate the DNA synthesis?
DNA polymerase and DNA ligase
what does this allow?
addition of a new and properly matched nucleotide base that is a complementary base to the template strand
what is another mechanism of DNA repair?
Nucleotide excision repair
what mechanism does it resemble?
the mismatch repair mechanism
mismatch repair corrects how many nucleotide pair mismatches?
one
how many mismatch paris does nucleotide excision repair correct?
can remove and replace more than one damaged nucleotide bases
what do the damaged bases do?
signal to specific enzymes to cleave the DNA backbone on either side or flanking the region of damaged or mismatched bases
what happens after removal?
DNA synthesis is able to completely fill the excised gap with correctly matched and complementary nucleotides to the template strand
are there various types of mutations that escape repair and can be found in our genome?
yes
what types of mutations can appear?
small point mutations or larger scale mutations
what are small point mutations
involve signal nucleotide pair changes in a DNA sequence
what are larger scale mutations?
involve changes in large regions of chromosomes
when can small scale point mutations arise?
during DNA replication
which mutations are able to become a permanent change in our genome?
mutations that escape the proofreading mechanism of DNA replication
what is the most common type of point mutation?
single nucleotide pair substitution
what is this?
where only one base pair is incorrectly replaced by another pair of nucleotides
what are these variations also known as?
single nucleotide polymorphisms SNPs
