DNA Repair Flashcards
What may break down DNA molecules?
Thermal degradation
Metabolic byproducts (like oxidation)
Evironmental substances like benzopyrene
Radiation - such as UV light and nuclear
What are purines and pyrimidines?
Purines are adenine and guanine
Pyrimidines are cytosine and thymine
They have similarities
The similarities between purines and pyrimidines?
Guanine and thymine (remember they are in different groups) but they both have carboxyl groups
Adenine and cytosine both have amine group
What exists between base pairs in the DNA double helix?
Hydrogen bonds
There are 3 between C and G
two between A and T
What is important to note about thymine and hydrogen bonding?
There is a methyl group which has doesn’t participate in methyl bonding.
What happens to cytosine in DNA damage? And how is this caused?
Water can cause cytosine to break down into uracil in a process called hydrolytic attacks
Remember uracil is good for DNA replication but bad in this instance
What is the problem when cytosine breaks down to uracil? What structure is uracil similar to?
When a cytosine becomes uracil due to DNA damage, it can no longer make adequate hydrogen bonding to guanine
Uracil is similar to thymine as both have a carboxyl group
Thus if cytosine breaks down to uracil, because its structure is similar to thymine, it binds to free floating adenines instead of guanines.
This leads to mutatuin
Cytosine deamination commonality?
Very common
What are all of the DNA bases susceptible to?
Oxidative attack or hydrolytic attack by water.
Another problem of cytosine becoming uracil?
In reference to new DNA strands
In DNA replication it causes new DNA strands to have an Adenine in the site where there should be a guanine
As the uracil binds to adenine but not guanine
This caused further mutation.
What are transition mutations?
When one purine mutates and becomes the other
Or when one pyrimidine mutates to become the other pyrimidine
Transversion mutation?
When a purine becomes a pyrimidine or visa versa
What is the most likely mutation to occur between the bases? and why?
Transition mutations are more likely
Because substituting one double ring for another double ring structure is more likely than substituting a double structure for a single ring structure
Note purines have a double ring structure and pyrimidines have a single ring structure
What is the structure of purines and pyrimidines in terms of ring structures?
Note purines have a double ring structure and pyrimidines have a single ring structure
Examples of transition mutations?
A -> G
C -> T
Transversion mutation examples:
A —> C or T
G —> C or T
C —> A or G
T —> A or G
Failure to repair DNA issues? And an example?
Causes mutations
An example is a frameshift mutation
This is when a purine or pyrimidine is lost from the DNA strand
In the example of DNA replication:
- an adenine may be lost from the template strand
- this means that the new strand doesn’t have a T as the base it binds to is missing
- these cause frameshift mutations
What can frameshift mutations cause?
They can lead to missense mutations - this causes different amino acids to be coded for due to changes
What is photolytic conversion? What do they involved?
Remember both thymine and cytosine have carbon carbon double bonds. These a pyrimidines remember
These are very vulnerable to light specifically UV light
Everytime you are in sunlight these double carbon bonds breakdown in the pyrmidines.
This causes two pyrimidines like two thymines to bind together and become stuck together.
This distorts the DNA structure affecting DNA rep
What is it called when two pyrimidines bind together due to photolytic conversion?
This is called DNA replication
What is important to note about DNA constantly under attack?
There is a selection pressure to repair
How do you overcome depurination? What is the pathway called and what are the three key enzymes involved?
This is when a cytosine becomes a uracil after losing a amine
You overcome this with the BER pathway
Glycosylase enzyme
- on each DNA strand there is a glycosylase enzyme which is a repair enzyme
- they move along the DNA strand
- if they detect a inappropriate base like uracil then the glycosylase removes a base
Endonuclease / phosphodiesterase
- you then have a phosphodiesterase which removes the DNA backbone
- this causes there to be a gap in the DNA
DNA liberase
- this gap has a small substrate for DNA liberase to bind to
- this allows for insertion of the correct base which isnt uracil
How do BER glycosylases work?
- They use a base flipping strategy to identify errors
- they flip the incorrect base out by checking if the base fits its active site. If the base does then it is removed.
How are pyrimidine dimers fixed?
Remember these dimers are caused by photolytic conversion from uv light when the carbon carbon double bond of adjacent pyrimidines becomes hydrolysed. This causes pyrimidines like C and T to become bound together.
An excision nuclease comes along and recognises the pyrimidine dimers
These then cut out 12 base pairs of the DNA sequence around the pyrimidine dimers to remove it.
DNA helicase then separates this small double stranded
DNA polymerase plus DNA ligase then synthesises the correct sequence again removing the pyrimidine
This is also called long patch base excision or nucleoside excision repair.
