in this video we'll talk about zero Dharma pigmentosum zero gamma pigmentosum is a very rare skin disorder where people are highly sensitive to UV damage and they don't have a good repair system the risk genes include xpa xpc D G and F so all of these genes are actually involved in the UV repair system so these are component of nucleotide repair system so in this particular disease the person get high exposure from the UV rays there could be DNA damage due to the UV rays but it is not repaired in an optimal fashion and that
lead to many complications and most worst case scenario is skin cancer when genetics is concerned this particular disease is autosomal recessive in nature that means there is a 25 percent of chance that in the Next Generation somebody would be affected by this disease symptoms include thinning of the skin visible broken blood vessels dry and red eye potential skin cancers dark and light patches of pigmented skin then sensitive towards light especially sunlight so in order to understand the biology behind this disease we have to understand the process of nucleotide excision repair in bit more details nucleotide
excision repair protects our DNA from UV damage when there is a UV damage it forms this kind of dimers so thymine thymine dimer is a common lesion caused by UV radiation and this kind of you thymine dimer can distort the DNA architecture and this has to be repaired and there are set of proteins that can sit and repair this kind of damages caused by harmful UV radiation and that system is known as nucleotide excision repair system this particular system is well conserved from bacteria to human so let us understand this process in bacteria first for
Simplicity and then we'll extrapolate to Human so imagine there is a dimer in this so the dimer is recognized by uvr ape and uvrb protein eventually the DNA lesion uh is kind of recognized by this set of protein Machinery uvr loads uvrb in the recognition site eventually ATP is hydrolyzed and uvrb cause a bend in the DNA then uvrc gets loaded eventually it creates Nick in the DNA and there is a helicase uvrd which leads to chopping off that portion of the Strand this is known as the excision so after excision a portion of the
Strand is basically now single stranded and open hydroxyl end is produced there so in that case specific polymerase polymerizes this particular damage and at the end Gap is sealed by a ligase enzyme so this General proforma that means excision followed by the repair is pretty similar in human and bacteria so this was in bacteria in human these uvr a proteins are actually known as xpc xpd xpd creates a bubble around the particular lesion then there are also RPA proteins which hold the strands there are ercc one xpf protein that creates the Nick and there are
xpg proteins so all of these proteins are analogous to the uh E coli protein anyway this particular kind of repair system works hand in hand with the transcription machinery so transcription actually the RNA polymerase recruit this kind of this kind of DNA repair Machinery to the site of lesion and the lesion is repaired and transcription can be resumed so that is why this particular transcription uh this couple transcription coupled repair is very important for the disease etiology now if this particular repair is abrogated then there are high risk of accumulating mutations there are also risk
of changing gene expression modulation because these repair system goes hand in hand with transcription and that leads to many complications and the most worst is the cancer so the treatment option includes protective gears like UV protective jackets caps sunglasses and sunscreen and the prevention is better than cure so staying at home in a protective environment where you are not exposed to UV light is the solution right now there is no definitive cure for this disease managing this particular disease with proper treatment and Care is the only option I hope this was useful if you like
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