UVA jacks up your DNA, in an indirect manner...sort of...

Sep 17 2011 Published by under Uncategorized

This post is in response to a buddy asking me about the effects of UVA on the skin.

The ultraviolet rays are subdivided into three categories:  UVA, UVB, UVC.  The most energetic and damaging form of UV radiation to our cells comes in the form of UVC.  Luckily the majority of UVC rays from the sun are absorbed by our planets ozone layer*.  Unlike UVB, which can be absorbed by the DNA and cause direct damage, UVA for the most part is unable to cause direct DNA damage.  However this doesn't mean that it can't still screw up your DNA and it does this by generating reactive oxygen species (ROS).  ROS can react with your DNA to form 8-oxoguanine, which cause G to T transversion mutations by the mispairing of adenine with the 8-oxoguanine lesion.  Luckily for us this lesion is rapidly repaired through the base excision repair pathway using a special enzyme called Oxyguanine Glycosylase (OGG).

OGG works by "getting it in" with the DNA to loosely use some Jersey Shore language.  What happens is a key residue inserts into the double helix, causing the damaged base to flip out.  Following this OGG cleaves the glycosyl bond leaving the sugar phosphate backbone of DNA intact but the end result is the base gets clipped out, creating what is called an abasic site.  The strand is then nicked by an AP endonuclease which creates a gap that allows the DNA polymerase (usually Pol Beta) to fill in the gap.  After a little end processing and ligation the DNA is good as new.

Another form of damage thought to be caused by UVA damage is the cyclopyrimidine dimer (CPD), in particular the thymine dimer**.  This is a more serious lesion that can create problems especially as it can create roadblocks for replication and transcription, putting your genomic stability in peril. CPDs are repaired by a process called nucleotide excision repair which operates in two different modes.  One is called global genome repair (GG-NER) whereby the repair proteins are scanning the DNA for lesions and repairs them when encountered.  The other is called transcription coupled repair (TC-NER) which is more of a situation that is analogous to you showing up to work and getting ready to start using a piece of equipment but its broken.  So as the cell is transcribing the DNA in order to create RNA it encounters the CPD lesion and fixes it then.  So NER operates in these two modes:  the reactive (TC-NER) and the proactive (GG-NER model).

The NER pathway works first by damage recognition as the CPD lesion distorts the helix and that is what the initial repair proteins key in on.  The DNA is then unwound by helicases resulting in two pieces of single stranded DNA that must be coated by proteins in order to prevent degradation, and then a 24-27 nucleotide fragment around the lesion is incised on both ends by nucleases.  Following this a DNA polymerase fills in the gap and its ligated together.  Not so bad, but it would be a hell of a lot easier on your cells if you'd just wear your sun screen so they don't have to do this.

UVA can also cause single strand breaks in the DNA which left unrepaired can form double strand breaks, this can lead to chromosomal aberrations and turn a normal cell into a cancerous one.

*A reference your grand-kids will have no idea about probably.

**This is still being debated in the literature.

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