Enhanced nucleotide excision repair in human fibroblasts pre-exposed to ionizing radiation.
Cellular protection against deleterious effects of DNA damaging agents requires an intricate network of defense mechanisms known as the DNA damage response (DDR). Ionizing radiation (IR) mediated activation of the DDR induces a transcriptional upregulation of genes that are also involved in nucleotide excision repair (NER). This suggests that pre-exposure to X-rays might stimulate NER in human cells. Here, we demonstrate in normal human fibroblasts that UV-induced NER is augmented by pre-exposure to IR and that this increased repair is accompanied by elevated mRNA and protein levels of the NER factors XPC and DDB2. Furthermore, when IR exposure precedes local UV irradiation, the presence of XPC and DDB2 at the sites of local UV damages is increased. This increase might be p53 dependent, but the mechanism of X-ray specific stabilization of p53 is unclear as both X-rays and UV stabilize p53.
Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.
Patricia
P
Cramers
Alfred Ronald
AR
Filon
Alex
A
Pines
Jos C
JC
Kleinjans
Leon H F
LH
Mullenders
Albert A
AA
van Zeeland
D001483:Base Sequence; D017931:DNA Primers; D004260:DNA Repair; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers