TY - JOUR
T1 - Sturcture and expression of the human XPBC/ERCC-3 gene involved in DNA repair disorders xeroderma pigmentosum and cockayne's syndrome
AU - Weeda, Geert
AU - Ma, Libin
AU - Van Ham, Reinier C.a.
AU - Van Der Eb, Alex J.
AU - Hoeijmakers, Jan H.J.
N1 - Funding Information:
We would like to thank Dr. H. van Ormondt for critically reading this manuscript, Prof. D. Bootsma for his stimulating interest and support, and R. Masurel for technical assistance, M. Kuit for photography and Mrs. R.J. Boucke for skilful typing. We thank Dr. P. Herrlich (Karlsruhe, FRG) for providing the MTTIA cDNA clone and S. Gibson and C. Backendorf for gift of RNA from (UV)-exposed keratinocytes. The work was financially supported by the Netherlands Organization for Advancement of Pure Research (NWO) through the Foundation of Medical Scientific Research (contract no. 900-501-091) and EURATOM (contract no. BJ6-141-NL) and by the Dutch Cancer Society (OCR 90-20).
PY - 1991/11/25
Y1 - 1991/11/25
N2 - The human XPBC/ERCC-3 was cloned by virtue of its ability to correct the excision repair defect of UVsensitive rodent mutants of complementation group 3. The gene appeared to be in addition implicated in the human, cancer prone repair disorder xeroderma pigmentosum group B, which is also associated with Cockayne's syndrome. Here we present the genomic architecture of the gene and its expression. The XPBC/ERCC-3 gene consists of at least 14 exons spread over approximately 45 kb. Notably, the donor splice site of the third exon contains a GC instead of the canonical GT dinucleotide. The promoter region, first exon and intron comprise a CpG island with several putative GC boxes. The promoter was confined to a region of 260 bp upstream of the presumed cap site and acts bidirectionally. Like the promoter of another excision repair gene, ERCC-1, it lacks classical promoter elements such as CAAT and TATA boxes, but it shares with ERCC-1 a hitherto unknown 12 nucleotide sequence element, preceeding a polypyrimidine track. Despite the presence of (AU)-rich elements in the 3′-untranslated region, which are thought to be associated with short mRNA half-life actinomycin-D experiments indicate that the mRNA is very stable (t 1/2<3h). Southern blot analysis revealed the presence of XPBC/ERCC-3 cross-hybridizing fragments elsewhere in the genome, which may belong to a related gene.
AB - The human XPBC/ERCC-3 was cloned by virtue of its ability to correct the excision repair defect of UVsensitive rodent mutants of complementation group 3. The gene appeared to be in addition implicated in the human, cancer prone repair disorder xeroderma pigmentosum group B, which is also associated with Cockayne's syndrome. Here we present the genomic architecture of the gene and its expression. The XPBC/ERCC-3 gene consists of at least 14 exons spread over approximately 45 kb. Notably, the donor splice site of the third exon contains a GC instead of the canonical GT dinucleotide. The promoter region, first exon and intron comprise a CpG island with several putative GC boxes. The promoter was confined to a region of 260 bp upstream of the presumed cap site and acts bidirectionally. Like the promoter of another excision repair gene, ERCC-1, it lacks classical promoter elements such as CAAT and TATA boxes, but it shares with ERCC-1 a hitherto unknown 12 nucleotide sequence element, preceeding a polypyrimidine track. Despite the presence of (AU)-rich elements in the 3′-untranslated region, which are thought to be associated with short mRNA half-life actinomycin-D experiments indicate that the mRNA is very stable (t 1/2<3h). Southern blot analysis revealed the presence of XPBC/ERCC-3 cross-hybridizing fragments elsewhere in the genome, which may belong to a related gene.
UR - http://www.scopus.com/inward/record.url?scp=0026008883&partnerID=8YFLogxK
U2 - 10.1093/nar/19.22.6301
DO - 10.1093/nar/19.22.6301
M3 - Article
C2 - 1956789
AN - SCOPUS:0026008883
SN - 0305-1048
VL - 19
SP - 6301
EP - 6308
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 22
ER -