Mutagens, Mutations and their Prevention Flashcards
What is a mutagen?
An agent capable of increasing the frequency of mutation. Different mutagens have different effects, they cause different mutations in the DNA. Most work by altering base-pairing properties in the DNA.
What is EMS, and how does it act as a mutagen?
EMS is an alkylating agent, moves an ethyl group from one compound to another. In DNA the EMS adds an ethyl group to the base guanine. The ethyl group interrupts the normal formation of 3H bonds between G and C. Polymerase will instead add a base that undergoes 2H bonds, such as thymine. Once the strand with the incorrect base bair is then replicated, the base pair has been fundamentally changed (CG goes to TA) and mutation has occurred.
What is 2-amino purine, and how does it act as a mutagen?
It is a base analogue, meaning it can substitute as the base adenine, and undergo base-pairing most usually with thymine but can also bind with cytosine. When it binds with cytosine it leads to base pairing A-C, and eventually C-G upon replication.
What is aflatoxin, and how does it act as a mutagen?
Produced by fungi, and can enter the cell and interact with DNA. Aflatoxin can bind to the nitrogen site of guanine. This interrupts the bond between the deoxyribose sugar and the base, generating aprunic sites. This appears as a ‘blank’ during DNA replication, often times a base (adenine) is inserted opposite the black. Upon another round of replication this may result in a mutation.
What are ‘Bypass’ DNA polymerases, and how can they act to cause mutations?
Can be considered to be ‘low-fidelity’ DNA polymerases, which can replicate past damaged DNA sequences, unlike standard DNA polymerases. These polymerases are also much more likely to incorporate incorrect bases, possibly resulting in mutation.
What is the standard way to repair mutagen ‘damage’?
Mutations did not occur until the altered sequence has undergone a round of replication. So you can think of it as pre-mutgenic lesions, and then a mutation upon replication. Repair takes place on the pre-mutagen lesions, past this point it is too late.
How is EMS damage repaired?
Alkyltransferases are utilised, they recognise additional ethyl groups on the modified guanine bases and will remove it from the DNA, standard base-pairing will commence at this stage.
How are aprunic sites dealt with?
AP endonuclease, an enzyme, recognises an aprunic sites in the DNA sequence and cuts the sequence where it is contained. Excision exonucleases then degrade the defective DNA as well as surrounding sequences, can then be repaired by DNA polymerase. (Excision repair)
How does radiation result in mutations?
Neighbouring thymine bases can become covalently crosslinked photo-dimers. Prevents standard base-pairing between adjacent bases.
How is photo-dimerisation repaired?
Multiple ways to achieve the repair, one being nucleotide excision, similar to repair of aprunic sites. Can also utilise the photolyase enzyme, which uses energy from white light to convert photodimers back to pyrimidines so standard base-pairing can occur.
