Global genome repair is required to activate KIN17 , a UVC-responsive gene involved in DNA replication

Abstract

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 UVCinduced 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.melanoma ͉ XPA ͉ XPC ͉ genotoxic stress ͉ nuclear proteins

The involvement of XPC protein in the cisplatin DNA damaging treatment-mediated cellular response

“…The XPC protein recognizes a variety of bulky DNA damages including UV-caused cyclobutane pyrimidine dimers and cisplatin-generated interstrand crosslinks (ICL) [9][10][11][12][13][14][15][16]. The XPC protein binds tightly with an HR23B protein to form a stable XPC-HR23B complex [17][18][19].…”

A Tandem of SH3-like Domains Participates in RNA Binding in KIN17, a Human Protein Activated in Response to Genotoxics

“…It is up-regulated following DNA damage produced by UV-C or by ionizing radiation, 1,2 and this response to UV light is strictly dependent on the presence of the functional nucleotide excision repair proteins XPA and XPC. 2,3 The ectopic overexpression of gene KIN17 modifies the nuclear morphology and inhibits S-phase progression, thus blocking cell growth. 4,5 KIN17 encodes for a nuclear protein conserved from yeast to human.…”

KIN17 encodes an RNA-binding protein and is expressed during mouse spermatogenesis

“…In adult mouse tissues this gene is ubiquitously expressed at a low level (Tissier et al, 1996). KIN17 is a nuclear protein of 45 kDa conserved from yeast to human which is up-regulated after UV and γ irradiation Blattner et al, 2000;Kannouche et al, 1998;Masson et al, 2001;Masson et al, 2003). The structures of E. coli RecA and KIN17 proteins are different, but nevertheless share an epitope of 40 residues belonging to a DNA-binding domain located in the C-terminal end of RecA protein and in the core of KIN17 protein (Kurumizaka et al, 1996;Mazin et al, 1994a).…”