DNA damage and repair Flashcards
What can damage DNA?
CHEMICALS (carcinogens): dietary, lifestyle, environmental, occupational, medical and endogenous
RADIATION: ionising, solar and cosmic
….
- Most chemicals we are exposed to must be metabolically converted to something that can damage DNA
- 40-45% of all human cancer is associated with diet (eating AND drinking)
- Lifestyle choices we make massively affect what we are exposed to (e.g. smoking and ethanol)
- Herbicides and pesticides contribute to a relatively small proportion of the human cancer burden
- Medical treatments, such as radiotherapy, can also damage DNA and increase the risk of cancer
Give an example of an endogenous process that could damage DNA
Mitochondria produce reactive oxygen species that may damage DNA
What are the ways in which carcinogens may damage DNA?
- base hydroxylation
- abasic sites
- single stand breaks
- double strand breaks
- DNA adducts and alkylation
- base dimers and chemical cross links
What are base dimers/chemical cross links?
DNA molecules are chemically linked together
What is base hydroxylation?
An oxidative reaction occurring on one of the DNA bases. This means that the DNA has to be repaired and in the process may be mutated
What are abasic sites?
During the repair process, the entire DNA base has been removed - during replication this will cause problems
What are single strand breaks?
These are very common and can be very useful. There are physiological enzymes that are responsible for making single strand breaks. Topoisomerase is involved in the relaxing and unwinding of DNA. It works by chopping the strand of DNA and allowing it to unwind and we can gain access to the DNA, as the strand is re-annealed. So we can deal with single strand breaks in DNA.
What are double strand breaks?
These are a bit of a disaster. After the double strand breaks, there is a tendency for the two bits of DNA to drift apart and this is intolerable from the cell’s point of view. There are a number of DNA repair mechanisms that attempt to amend this, but sometimes the DNA repair can go wrong and introduce DNA damage.
What are DNA adducts and alkylation?
This is generally the type of damage that is caused by chemicals. Some chemicals tend to be metabolically activated into electrophiles, DNA is very rich in electrons because of all the nitrogens in the bases. The electrophiles bind to the DNA and form a covalent bond. The binding of a big bulky chemical to the DNA causes problems particularly during replication because the DNA polymerase runs along the strand and wants to figure out which base to put in next, but it wont be able to do this if it is bound to a big chemical group. In short, DNA polymerase cannot recognise the base because of the chemical adduct.
What are polycyclic aromatic hydrocarbons?
- Common environmental pollutants
- Formed from the combustion of fossil fuels
- Formed from the combustion of tobacco
They are found in smoke - it is poisonous- are DNA damaging
