Xeroderma pigmentosum


Xeroderma pigmentosum, XP, is a rare heterogeneous genetic disorder with an occurence rate of approx. 1 in 250,000. The disorder entails defective UV-radiation damage repair, normally characterized by extreme photosensitivity, pigmentary alterations such as freckles, as well as evident eye damage and skin burning when the epidermal skin layer of the affected individual is exposed to minimal amounts of UV radiation.
Our mammalian genome is continually being damaged and affected by an endless variety of environmental agents such as UV, ionizing agents and genotoxic chemicals such as benzene. UV radiation induces two primary categories of photolesions: photoproducts of cyclobutane pyrimidine (CPD) and pyrimidine (6-4) pyrimidone ((6-4) PP). These are the predominant forms of premutagenic damage after sun exposure 1. In the absence of repair, these DNA lesions remain in the genome, resulting in mutagenesis, implicated in the development of skin cancer.

XP is primarily caused by an autosomal recessive genetic defect in where by nucleotide excision repair (NER) enzymes are mutated, prompting a reduction in or destruction of NER. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die. XP patients have more than a 10,000-fold increased risk of developing skin cancer.
There are 8 XP genes. The seven first genes (XPA to XPG) are related with the nucleotide excision repair (NER), that is the major mechanism able to fix the DNA damages caused by UV in humans and they all lead to the disease however they all differ. For example, XPC, an XP gene, encodes a component of NER. It carries out a significant role in the premature steps of global genome NER (GG-NER), predominantly related to damage recognition and repair protein complex, XP-C, formation.