Xeroderma Pigmentosum Research Paper

Xeroderma Pigmentosum (XP) is an inherited recessive disease, this means two recessive alleles are present in an individual from their parents. This disease impairs the ability of the body to repair DNA which is damaged mainly by Ultraviolent light as well as various chemical Carcinogens. ” The most common forms of DNA damage occurs via the cross linking of adjacent pyrimidines resulting in the formation of cyclobutane pyrimidine dimers (CPDs)” (1) for example UV light will often make two T 's bases next to each other bind making a dimer.

The regions of the cells that are affected by the disease are called the nucleotide excision repair (NER) enzymes. There are two types of NER that exist: global genome (GG-NER) and transcription coupled
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The XPA gene is responsible for providing instructions for making proteins that are involved in repairing damaged DNA. XPB has the same type of mutation as XPA however it is an essential subunit of a 9 unit general transcription factor IIH (TFIIH) complex. The TFIIH complex helps repair damaged DNA therefore mutation in XPB means the TFIIH complex doesn’t form properly hence cannot do its job. In XPC there is a single base substitution on the third chromosome this causes a missense mutation which produces inactivated XPC protein this is crucial because XPC proteins start NER process by detecting DNA damage in the GG-NER pathway. Therefore without the XPC protein DNA repair process cannot be started as the damaged DNA isn’t identified by the body. The XPD gene is found on chromosome 19. XPD is involved with working with the XPB gene to form TFIIH complex. TFIIH is involved in the regulation of transcription of active genes, as well as in NER (4)(5). Therefore if the TFIIH complex does not form correctly this could possibly alter the rate of transcription for example, increasing it which would cause exponential cell growth and this could be a reason why people who have XP are much more like to develop cancer. XPV is a variant of XP and does not affect NER. Instead, there is a defect in DNA polymerase which alters post …show more content…
There a few different theories as to how neurodegeneration occurs such as due to the lack of an effective NER pathway the mutations in “DNA can have effects on post-mitotic neurons and cause severe CNS symptoms” (4) and “It is most likely that there are some forms of oxidative damage for which NER is also the repair pathway, just as there are likely to be other forms where resolution will involve DNA strand break repair” (9). However the exact process of how neurodegeneration occurs is still unknown. The key variations of XP that cause neurodegeneration are XPA, XPD and XPG , which XPG having the most severe effect. Some neurological problems that occur from XP are loss of hearing, hyporeflexia, progressive mental retardation, poor co-ordination and seizures.
There are several ways to suppress the symptoms of XP such as to limit exposure to direct sunlight, however if this is not possible then, the use of sunscreens with a SPF of 15 or greater and other sun-avoidance methods e.g., protective clothing can minimize UV damage. Cryosurgery is the use of liquid nitrogen to freeze cancer cells, which kills the cancer cell however this can only be used to treat cancers that are not large or deep. Conventional treatments can also be used such as chemotherapy and Mohs surgery

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