Global genome repair is required to activate KIN17, a UVC-responsive gene involved in DNA replication.
UV light provokes DNA lesions that interfere with replication and transcription. These lesions may compromise cell viability and usually are removed by nucleotide excision repair (NER). In humans, inactivation of NER is associated with three rare autosomal recessive inherited disorders: xeroderma pigmentosum (XP), Cockayne syndrome, and trichothiodystrophy. The NER earliest step is lesion recognition by a complex formed by XPC and HHR23B proteins. In a subsequent step, XPA protein becomes associated to the repair complex. Here we investigate whether XPA and XPC proteins, involved in global genome repair, may contribute to a signal transduction pathway regulating the response to UVC-induced lesions. We monitored the expression of several UVC-induced genes in cells deficient in either a transduction pathway or mutated on an NER gene. Expression of the KIN17 gene is induced after UVC irradiation independently of p53 and of activating transcription factor 2. However, in human cells derived from XPA or XPC patients the UVC-induced accumulation of KIN17 RNA and protein is abolished. Our results indicate that the presence of functional XPA and XPC proteins is essential for the up-regulation of the KIN17 gene after UVC irradiation. They also show that the integrity of global genome repair is required to trigger KIN17 gene expression and probably other UVC-responsive genes.
Masson
Christel
C
Laboratoire de Génétique de la Radiosensibilité, Département de Radiobiologie et de Radiopathologie (DRR), Direction des Sciences du Vivant (DSV), Commissariat à l'Energie Atomique (CEA), B.P. 6, 92265 Fontenay aux Roses, France.
Menaa
Farid
F
Pinon-Lataillade
Ghislaine
G
Frobert
Yveline
Y
Chevillard
Sylvie
S
Radicella
J Pablo
JP
Sarasin
Alain
A
Angulo
Jaime F
JF
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008545:Melanoma / Q000235:genetics; D016685:Mitomycin / Q000494:pharmacology; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C489487:KIN protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human; D016685:Mitomycin