Enhanced nucleotide excision repair in human fibroblasts pre-exposed to ionizing radiation. 2012

Patricia Cramers, and Alfred Ronald Filon, and Alex Pines, and Jos C Kleinjans, and Leon H F Mullenders, and Albert A van Zeeland
Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.

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.

UI MeSH Term Description Entries
D011839 Radiation, Ionizing ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays. Ionizing Radiation,Ionizing Radiations,Radiations, Ionizing
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D017931 DNA Primers Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques. DNA Primer,Oligodeoxyribonucleotide Primer,Oligodeoxyribonucleotide Primers,Oligonucleotide Primer,Oligonucleotide Primers,Primer, DNA,Primer, Oligodeoxyribonucleotide,Primer, Oligonucleotide,Primers, DNA,Primers, Oligodeoxyribonucleotide,Primers, Oligonucleotide
D020133 Reverse Transcriptase Polymerase Chain Reaction A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. Polymerase Chain Reaction, Reverse Transcriptase,Reverse Transcriptase PCR,PCR, Reverse Transcriptase,Transcriptase PCR, Reverse

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