DNA Damage Flashcards
(29 cards)
Our DNA is under chemical and physical assault.
Name some of the common problems.
Ionizing Radiation
Spontaneous Depurination
Spontaneous Deamination
Thymidine Dimer Formation
Oxidation of Bases
What is Ionizing Radiation?
Breaking of phosphodiester linkages
Deletions of small segments of DNA from within a gene
What is Spontaneous Depurination?
Loss of purines from DNA (A and G)
Spontaneous Depurination
When a purine bass is lost, what is the site called?
Bond that holds purine bases to sugar is quite vulnerable to hydrolysis (A and G)
The loss of a purine case creates an APURINIC site (AP site)
What is the problem with an apurinic site?
The AP site has to be corrected or else the DNA cannot serve as a template o make DNA or RNA (because there is no nitrogenous base to pair with)
What is Spontaneous Deamination?
Removal of amino group from cytosine
What is the result of the removal of the amino group from cytosine?
If the amino group is removed from C, it produces Uracil.
If U remains, then it will serve as a template to add A (instead of G)
What is Thymidine Dimer Formation?
UV light causes production of thymine dimers
These dimers can occur when two T bases are adjacent to each other on the same strand
What is the consequence of thymidine dimer formation?
Thymine dimers can block DNA synthesis so they must be removed for a cell to divide.
Thymidine dimer formation happens all the time in sunlight.
What are the two diff systems for removing thymidine dimers?
- enzyme called photolyase recognizes thymine dimers with the help of a light absorbing chromophore breaks the covalent bond holding the dimers together, this restores both thymidine bases to their normal structure
- nucleotide excision repair system
True or False: Reactive oxygen species are by products of our aerobic metabolism.
True - Reactive oxygen species are by products of our metabolism.
What is an example of oxidation of bases?
Which base does this usually happen?
Addition of oxygen to our nucleotides
Usually happens in guanine
- G can be transformed by an oxidizing agent into GO
Oxidation of Bases
Why does the GO base cause mutations?
The GO base, if left in the DNA, causes mutation because it can hydrogen bond quite well with adenine (instead of guanine’s normal partner cytosine - G and C).
What are two mechanisms of repair?
Base excision repair system
Nucleotide excision repair system
What are mutagens
Mutagens - chemicals/energy sources that raise frequency of mutation above naturally occurring frequency
How can we test for mutagenicity BEFORE humans etc are exposed to them?
In other words how do we identify chemicals that might be mutagens and not allow them to be in our foods, drinking water, etc.
AMES Test
Describe the AMES test.
- Ames took the rapidly growing bacteria, Salmonella
- Control: WT that can make histidine
- other strains where limitations are placed (can’t make histidine, removal of protective coat, knocked out several repair systems)
- -> so we can measure reverse mutation (non-WT to WT)
What are the major categories of mutagens?
High Energy Radiation
Base Analogs
Chemical Modifiers of otherwise normal bases
Intercalating agents
MUTAGENS
Chemical Modifiers of otherwise normal bases
Hydroxylating agents
Alkylating agents
Deaminating agents
MUTAGENS
What are Base Analogs?
These are compounds that resemble bases and can be incorporated into DNA.
But the incorporation can lead to incorrect DNA sequences being replicated.
MUTAGENS
What are Intercalating Agents?
Intercalating agents are flat cyclical molecules that are roughly the same shape as a base pair.
They can stack in between base pairs.
What are some DNA Repair Mechanisms?
- Proofreading ability of DNA polymerases
- Mismatch repair
- Removal of thymidine dimers by photolyase
DNA Repair Mechanisms
Removal of thymidine dimers by photolyase
Simplest system to remove thymidine dimers is with the enzyme photolyase
- Photolyase bins to the thymidine dimer and w/ the help of chromophor molecule, it absorbs some of the energy form the sunlight and uses that energy to break the covalent bond linking the two thymidines (returning them to their normal state)
Thymidine dimers readily form in _____.
So it is good to have two different repair systems to remove them. What are the two repair systems called?
Thymidine dimers readily form in sunlight.
