ERCC2 : ERCC excision repair 2, TFIIH core complex helicase subunit

Description

The ERCC2 (ERCC excision repair 2, TFIIH core complex helicase subunit) is a protein-coding gene located on chromosome 19.

The ERCC2 gene provides instructions for making the XPD protein, a vital component of the TFIIH complex. The TFIIH complex has two primary functions: regulating gene transcription and repairing damaged DNA. Gene transcription is the first step in protein production, and the TFIIH complex helps control this process. The XPD protein appears to stabilize the TFIIH complex, working with the XPB protein (from the ERCC3 gene) to initiate gene transcription. TFIIH also plays a key role in DNA repair, particularly in nucleotide excision repair (NER). The XPD protein acts as a helicase, unwinding damaged DNA sections, allowing other proteins to remove the damaged portion and replace it with correct DNA.

The ERCC2 gene encodes the XPD protein, an ATP-dependent 5'-3' DNA helicase that is a core component of the general transcription and DNA repair factor IIH (TFIIH) complex. TFIIH is essential for both general and transcription-coupled nucleotide excision repair (NER) of damaged DNA. In NER, TFIIH acts by opening the DNA around a lesion, allowing for excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The helicase activity of XPD/ERCC2 is crucial for this DNA opening. TFIIH also plays a key role in transcription initiation. When the pre-initiation complex (PIC) has been assembled, TFIIH is required for promoter opening and promoter escape. The kinase module CAK, complexed with TFIIH, controls the initiation of transcription by phosphorylating the C-terminal tail (CTD) of RNA polymerase II's largest subunit. XPD/ERCC2 acts as a bridge between CAK and the core-TFIIH complex. Beyond DNA repair and transcription, ERCC2 has been implicated in the regulation of vitamin-D receptor activity. As part of the MMXD complex, it contributes to chromosome segregation during mitosis. ERCC2 may also play a role in the aging process and could potentially contribute to the development of skin cancers.

ERCC2 is also known as COFS2, EM9, TFIIH, TTD, TTD1, XPD.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing

Clinical Exome Sequencing