MBG Part Two: Lecture 12 Flashcards
How often do spontaneous mutations occur?
Very infrequently
How Many mutations are in bacteria cells?
1 in 100 per every 10 billion cells
How many mutations are in Eukaryotic cells?
1 - 10 mutations per every million gametes
What happens within genes?
Some are known to be more “hotspots” for mutations
What does the APC gene account for?
Account for greater than 80% of colon cancer - the MCR region in the gene is where most of the mutations occur.
What happens to DNA that is in nucleosomes?
Due to it being wrapped around histones, it may have more reduced exposure to mutagens.
What is the overall rate of a base substitution in humans?
1 x 10^-8 per base per generation
What does research suggest about each person and a loss of function gremlin mutation?
That each person carries about 100 loss of function germline mutations.
What are factors that affect mutation rate?
Frequency
Probability
Detection
What can cause DNA damage?
- UV light exposure
- Cellular Metabolism
- Ionizing Radiation
- Chemical Exposure
- Replication Error
What are “spontaneous mutations”?
When mutations occur under normal circumstances as a result of internal factors
What are “induced mutations”?
As a result of an exposure to external factors (i.e, chemicals)
What are spontaneous replication errors?
- Tautomeric Shifts
- Mispairing due to other structures
- Incorporated errors and replicated errors
- Insertions and Deletions
What are some spontaneous chemical changes?
- Depurination
- Deamination
- Methylated Cytosine
What are some chemical induced mutations?
- Base Analogs
- Alkylating Agents
- Deaminating Chemicals
- Hydrooxylamine
- Oxidative Radicals
- Intercalating Agents
What is radiation?
Energy released in the form of electromagnetic waves
In tautomeric shifts, what bases pair together?
A - C pairing (two hydrogen bonds)
T - G pairing (three hydrogen bonds)
What happens during mispairing of other structures?
It can arise through wobble, which can allow for flexibility in the DNA structure and any shifts in the helix can allow for different bases to bond
Can also arise by the protonated forms of the bases
What is incorporated errors?
Occur when a base substitution causes a mispaired base to incorporate into a newly synthesized strand
What does an incorporated mutation lead to?
A replication error that causes a permanent mutation
How can insertions and deletions happen?
From strand slipping or unequal crossing over during meiosis
What is strand slipping?
Strand slipping is when the template loops out which results in the omission of one new nucleotide
What is the unequal crossing over during meiosis?
The homologous chromosomes misalign and one crossover has an insertion and the other has a deletion.
What is depurination?
The loss of a purine base (G,A) from a nucleotide
What does depurination cause?
The breakage of the covalently bond between the purine base and the 1’ carbon atom of the deoxyribose sugar.
What does depurination lead to?
An apurinic site
What happens do to the apurinic site?
No complement base (it doesn’t know what the previous base was) so a random nt is incorporated (usually an A) which leads to a mutant
What is Deamination?
Loss of an amino group (typically from cytosine)
What does the demaintion of cytosine lead to?
Uracil which will pair with Adenine during replication. And in the next cycle A will pair with T, resulting in a C to T transition
What is a methylated cytosine?
Leads to the conversion of cytosine to thymine transition
What are base analogs?
Molecules with similar structures to the normal standard 4 nucleotides
What is 5BU?
An analog of Thymine, which pairs with Adenine but can also pair with Guanine
What is 2AP?
A base analog of Adenine, can mis pair with Cytosine (T to C transition)
What are Alkylating Agents?
Mutagens that can react with DNA bases and add methyl or ethyl to them
What are examples of Alkylating Agents?
Ethylmethylsulfonate (EMS) and Mustard Gas
What happens when the alkylating agents add an ethyl to guanine?
It can base pair with thymine
G to A transition
What happens when the alkylating agents add an ethyl to thymine?
It can base pair with guanine
T to C transition
What are examples of Deaminating Chemicals?
Nitrous Acid
What can Nitrous Acid change?
Cytosine to Thymine
Adenine to Hypothoxanthine, which can base pair with cytosine
Change guanine to Xanthine, which can base pair with Thymine
What is hydrooxylamine?
- Adds a hydroxyl to cytosine (increases rate of pairing with adenine)
C to T transition
What are oxidative Radicals?
Reactive forms of oxygen
What can Oxidative Radicals Cause?
G to T transversion
What are examples of Intercalating Agents?
Ethidium Bromide, Acridine Orange, Dioxin, Proflavin
What do intercalating agents do?
Sandwich themselves between base pairs which distorts the DNA helix
What do intercalating agents lead to?
Insertions and Deletions which cause frameshift mutations
What does radiation cause?
Causes a stable atom top turn into a free radical reaction ion and breaks phosphodiester bonds leading to double stranded breaks
What bases absorb UV light?
Pyrimidine bases
What does the absorbance of UV light cause?
Induces chemical bonds between two adjacent pyrimidine molecules
What dimers are most frequent with the induced chemical bonds?
Thymidine Dimers
