Xeroderma recessive genetic defect in where by nucleotide

Xeroderma pigmentosum, XP, is a rare recessive heterogeneous genetic disorder with an occurence rate of approx. 1 in 250,000 in the U.S. and 1 in 500,000 in Western Europe .

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. 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 first 7 genes (XPA to XPG) relate to nucleotide excision repair (NER), the major mechanism able to fix the DNA damages caused by UV in humans. For example, XPC, an XP gene, encodes a component of NER.

Don't waste your time
on finding examples

We can write the essay sample you need

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. Our human genome is continually 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: cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts ((6-4) PP). These are the predominant forms of premutagenic damage after sun exposure. Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions.

UV radiation promotes the development of covalent linkages between consecutive cytosine or thymine bases along the nucleotide chain in the proximity of their carbon–carbon double bonds. This leads to the distortion of the double helix and the introduction of bends and kinks on the double helical shape. This in turn impedes transcription and replication. The most common type of linkage, a thymine dimer, consists of two thymine bases that react with each other and become chemically linked. Approximately 50-100 reactions occur per second in a skin cell during UV exposure and they are corrected by NER. In the absence of repair, however, these DNA lesions remain in the genome, resulting in mutagenesis or XP.Additionally, it is now clear to that NER is a pathway used to remove and replace damaged base pairs.

In eukaryotes, NER relies on the products of around 30 genes and operates through 2 sub-pathways, depending on if the damage is located anywhere in the genome (GG-NER) or in an actively-transcribed gene (TC-NER). In the case of XP, GG-NER has a much greater role in repairing the body’s skin cells. For example, the most common cause of XP is the mutation of the XPC gene. The XPC gene is involved in GG-NER by acting as a damage sensing and DNA-binding factor component of the XP-C complex. The XP-C complex recognizes a wide spectrum of damaged DNA outlined by mutilations of the DNA helix such as single strand loops, mismatched bubbles or single strand overhangs.

The XPC complex binding orientation is thought to be crucial for generating a productive NER.


I'm Owen!

Would you like to get a custom essay? How about receiving a customized one?

Check it out