Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes.

Abstract

We have measured the removal of UV-induced pyrimidine dimers from DNA fragments of the adenosine deaminase (ADA) and dihydrofolate reductase (DHFR) genes in primary normal human and xeroderma pigmentosum complementation group C (XP-C) cells. Using strand-specific probes, we show that in normal cells, preferential repair of the 5' part of the ADA gene is due to the rapid and efficient repair of the transcribed strand. Within 8 h after irradiation with UV at 10 J m-2, 70% of the pyrimidine dimers in this strand are removed. The nontranscribed strand is repaired at a much slower rate, with 30% dimers removed after 8 h. Repair of the transcribed strand in XP-C cells occurs at a rate indistinguishable from that in normal cells, but the nontranscribed strand is not repaired significantly in these cells. Similar results were obtained for the DHFR gene. In the 3' part of the ADA gene, however, both normal and XP-C cells perform fast and efficient repair of either strand, which is likely to be caused by the presence of transcription units on both strands. The factor defective in XP-C cells is apparently involved in the processing of DNA damage in inactive parts of the genome, including nontranscribed strands of active genes. These findings have important implications for the understanding of the mechanism of UV-induced excision repair and mutagenesis in mammalian cells.

High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis

“…4 The XPC protein is involved in the first step of the nucleotide excision repair (NER); it is important in the recognition of target lesions and in the recruitment of the incision complex. 5 This human protein forms a strong heterotrimeric complex with Rad23B and centrin 2, and is involved in the recognition of UV ray-induced DNA lesions during global genome repair but not during transcription-coupled repair. [6][7][8] In vitro experiments have shown that the XPC complex might contribute toward cancer prevention by participating in the base excision repair of 8-OH-Gua and other oxidative DNA lesions.…”

p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene

“…Activity of XPC in NER requires its coactivating protein hHR23B (20), and the hHR23B interaction domain has been localized to a highly conserved region in the C-terminal half of XPC (21). Although the DNA lesion binding (12,15,22) and repair (16,18) properties of XPC have been characterized in some detail, much remains unknown about its regulation and mode of activation after DNA damage.…”

“…XPC cells are defective in removal of CPDs and 6-4 pyrimidine pyrimidone photoproducts from the global genome but repair CPDs selectively from the transcribed strand of active genes (16)(17)(18). Cheo et al demonstrated a similar defect in repair of 6-4PPs from the nontranscribed strand of the p53 gene in murine embryonic fibroblasts lacking functional XPC (19).…”

The xeroderma pigmentosum group C gene leads to selective repair of cyclobutane pyrimidine dimers rather than 6-4 photoproducts

“…It has been shown that cells from XPC patients are defective only in GGR and have normal TCR capability (8,(15)(16)(17). In 1992, the XPC gene was identified after transfection of XPC cells with a human cDNA expression library, resulting in correction of the severe UV sensitivity of these cells (18).…”