ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3.

Abstract

Human ERCC2 genomic clones give efficient, stable correction of the nucleotide excision repair defect in UV5 Chinese hamster ovary cells. One clone having a breakpoint just 5′ of classical promoter elements corrects only transiently, implicating further flanking sequences in stable gene expression. The nucleotide sequences of a cDNA clone and genomic flanking regions were determined. The ERCC2 translated amino acid sequence has 52% identity (73% homology) with the yeast nucleotide excision repair protein RAD3. RAD3 is essential for cell viability and encodes a protein that is a single‐stranded DNA dependent ATPase and an ATP dependent helicase. The similarity of ERCC2 and RAD3 suggests a role for ERCC2 in both cell viability and DNA repair and provides the first insight into the biochemical function of a mammalian nucleotide excision repair gene.

Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

“…Our amino acid sequence analysis indicates that ERCC5 is probably a nuclear-localized protein with one or more highly conserved helix-loop-helix (HLH) segments within domains A and B. We could find no sequence evidence in the ERCC5 protein for nucleoside triphosphate (NTP)-or Mg2e-binding domains associated with RNAIDNA helicases (32,66).…”

“…By using this method, human repair genes ERCC1, ERCC2 (XP-D), ERCC3 (XP-B), and ERCC6 (CS group B) have been sequenced and found to encode different deduced proteins (14,62,63,66,67). Conversely, mouse DNA complemented human XP-A cells, resulting in isolation of a functional mouse gene designated XPAC (58,59).…”

DNA repair, DNA replication and human disorders: A personal journey

“…We still do not really know the complete answer to this, though there have of course been some major advances. The first was the cloning of the ERCC2 gene by Christine Webber and Larry Thompson and demonstration that this was the XPD gene [61], the second was the seminal discovery by the group of Jean-Marc Egly in collaboration with the Rotterdam group that XPB and XPD were components of the transcription factor TFIIH, which had two functions, in NER and transcription [62]. Following on from these exciting findings we were able to identify the first mutations in the XPD gene, in TTD patients [63], and subsequently in many others and, importantly, we were able to show that each mutation site is disease-specific.…”

Comprehensive Assessment of Associations between ERCC2 Lys751Gln/Asp312Asn Polymorphisms and Risk of Non-Hodgkin Lymphoma

“…Excision repair crossing-complementing group 2 (ERCC2), also known as xeroderma pigmentosum complementary group D (XPD), functions in DNA unwinding during NER and basal transcription because it possesses single-strand DNAdependent ATPase and 5'-3' DNA helicase activities (Sung et al, 1993;de Boer and Hoeijmakers, 2000). ERCC2 gene which located at chromosome 19q13.3 comprises 23 exons and spans about 54, 000 base pairs (Weber et al, 1990;Itin et al, 2001). Single nucleotide polymorphisms (SNPs) of this gene are thought to engender structural alterations of NER pathway and influence cancer susceptibility.…”