ERCC2 Gene

The ERCC2 gene (ERCC Excision Repair 2, TFIIH Core Complex Helicase Subunit) is a protein coding gene located on chromosome 19q13.32. The ERCC2 gene functions as a DNA repair gene involved in double helix separation via a 5'-3' helicase activity. It forms part of the so-called "transcription factor II-human complex (TFIIH)" and is ATP-dependent. The TFIIH complex is known to be involved in the nucleotide excision repair (NER) pathway, which can repair DNA damage caused by chemotherapeutic treatment and basal transcription.

ERCC2 variants have been observed in a variety of cancers. A number of studies suggest that ERCC2 variants may function as biomarkers to predict response to neoadjuvant treatment and cancer prognosis.

The ATP-dependent helicase activity of XPD/ERCC2 is required for DNA opening. In transcription, TFIIH plays an essential role in transcription initiation. After formation of the preinitiation complex (PIC), TFIIH is required for promoter opening and exit. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls transcription initiation. XPD/ERCC2 forms a bridge between CAK and the core TFIIH complex. Involved in the regulation of vitamin D receptor activity. As part of the mitotic spindle-associated MMXD complex, plays a role in chromosome segregation. Possibly plays a role in the aging process and may play a causative role in the development of skin cancer.

Mutations in the ERCC2 gene can lead to three different diseases:

• Xeroderma pigmentosum Complementation group D
• Trichothiodystrophy
• Cockayne syndrome.

Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

1. Baden HP, Jackson CE, Weiss L et al (1976) The physicochemical properties of hair in the BIDS syndrome. Am J Hum Genet 28: 514-521.
2. Berneburg M, Krutmann J (2003) Xeroderma pigmentosum and related syndromes. Dermatologist 54: 33-40
3. Broughton BC et al (2001) Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene. Hum Mol Genet 10: 2539-2547
4. Liang C et al (2005) Characterization of tiger tail banding and hair shaft abnormalities in trichothiodystrophy. J Am Acad Dermatol 52: 224-232
5. Lund EB et al (2019) Novel ERCC2 mutation in two siblings with trichothiodystrophy.
6. Pediatr Dermatol 36:668-671.
7. Mondello C et al (1994) Molecular analysis of the XP-D gene in Italian families with patients affected by trichothiodystrophy and xeroderma pigmentosum group D. Mutat Res 314: 159-165
8. Price VH, Odom RB, Ward WH, Jones FT (1980) Trichothiodystrophy. Sulfur-deficient brittle hair as a marker for a neuroectodermal symptom complex. Arch Derm 116: 1375-1384
9. Rebora A (1987) PIBI(D)S syndrome-trichothiodystrophy with xeroderma pigmentosa (group D) mutation. J Am Acad Dermatol 16: 940-947.
10. Rebora A, Crovato F (1987) PIBI(D)S syndrome-trichothiodystrophy with xeroderma pigmentosum (group D) mutation. J Am Acad Dermatol 16: 940-947.
11. Richetta A et al (2001) What's new in trichothiodystrophy. J Eur Acad Dermatol Venereol 15: 1-4.
12. Sperling LC et al (2003) "Curly" wood and tiger tails: an explanation for light and dark banding with polarization in trichothiodystrophy. Arch Dermatol 139: 1189-1192
13. Toelle SP et al (2001) Trichothiodystrophy with severe cardiac and neurological involvement in two sisters. Eur J Pediatr 160: 728-731