How does UV radiation cause mutation in cells?
What is the mechanism? And how these mutations conserved in further replications of DNA?
I\’m conducting an experiment with algae, and I am using UV light to cause mutations, but I am a little unclear how the process actually works. After reading stuff on Wikipedia and looking through articles on Google scholar, I am a little frustrated and seek some clarity. Any help is appreciated!! Thanks.
UV 10
UV irradiation
You know that UV irradiation generates a wide range of photoproducts in DNA. Photons of UV light have sufficient energy to break some chemical bonds. The most prevalent DNA lesion induced by UV irradiation are the cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs)
DNA repair machinery exists to cope with these photolesions , and will fix the damage, either by using light to break the bonds between the pyrimidines, or by cutting out the section of the DNA strand that contains the dimer and using the sequence of the opposite strand to fill in the gap. However this system may be somewhat prone to error, leaving some dimers unrepaired
Persistent CPDs and 6-4PPs, , if not repaired in time , can have serious consequences at the moment of cell division. Before cell division, DNA needs to be replicated.
Replicative polymerases are highly stringent and stop when they encounter an UV induced CPD or 6-4PP. The frequency of lesions that block DNA synthesis is approximately the same as the frequency of these photoproducts.
Should these lesions persist, cells have to choose whether to undergo apoptosis and die, or survive at the cost of living with a modified genome.So, how can cells replicate their DNA when polymerase are blocked at the UV induced lesions?
It has been recently shown that, in order to minimize cell death resulting from replication blockage, cells have evolved a process known as Translesion Synthesis (TLS).
In this type of DNA synthesis a special kind of polymerases can use the UV damaged DNA as template and insert nucleotides opposite lesions.
These polymerase can be error-free or error-prone, depending of the type of polymerase involved.
The accurate (error free) human DNA polymerase eta (Pol?) evolved specifically to copy cyclobutane TT dimers by inserting the corrected complementary bases AA.
On the other hand, error prone polymerases are mutagenic and frequently incorporate incorrect nucleotides, generating mutations that can have severe phenotypic consequences for the cells.
The characterization of these polymerase have been described very recently. Their characterization took so long in part because these novel TLS polymerases are very different from classical replicative DNA polymerases, and some have proved to be particularly difficult to purify.
So, DNA is damaged by UV irradiation; at this point in order to minimaze cell death, error prone polymerase introduce mutations.
Of course the are other mechanisms involved…In addition of the mechanisms described above, when Cytosine is present in the CPD, a process of deamination takes places and Cytosine is transformed in Uracil.
In any case the message is:mutations are the result of the cellular responses to the UV damage.