XPD Helicase (3CRV)

From Proteopedia

Revision as of 20:15, 10 April 2016

XPD Helicase

Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).

Function

XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove damaged DNA due to UV exposure.

Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP.

Disease

Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). 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. CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. 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.

Structural highlights

References

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