XPD Helicase (3CRV)
From Proteopedia
(Difference between revisions)
| Line 10: | Line 10: | ||
== Disease == | == Disease == | ||
| - | The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) | + | The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>. |
CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. | CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. | ||
Revision as of 00:57, 27 April 2016
| |||||||||||
Proteopedia Page Contributors and Editors (what is this?)
Matt Kohler, Bashir Noor, Chih Hao Huang, Michal Harel, Mark Heslin, Shane Devlin
