A gene that regulates DNA replication in response to DNA damage is located on human chromosome 4q.
Inhibition of replicative DNA synthesis following gamma-irradiation is observed in eukaryotic cells but is defective in cells derived from patients with the cancer-prone inherited disorder ataxia-telangiectasia (A-T) and in A-T-like Chinese hamster cell mutants. Chinese hamster cells show a less pronounced inhibition of DNA synthesis after gamma-irradiation when compared to irradiated human HeLa or mouse A9 cells. Therefore, to identify new human genes involved in the regulation of DNA replication in response to ionizing radiation in mammalian cells, single human chromosomes were introduced into Chinese hamster cells by microcell-mediated chromosome transfer. It is found that a new gene on human chromosome 4q inhibits DNA synthesis following gamma- and UV irradiation in hamster cells. However, this delay of DNA replication did not improve cell survival or the level of chromosomal aberrations induced by X-rays, indicating that the lack of the inhibition of DNA synthesis after X-irradiation is not a prerequisite for the X-ray sensitivity and chromosomal instability, which is observed in A-T and A-T-like hamster cells.
D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations / Q000235:genetics; D002894:Chromosomes, Human, Pair 4; D006224:Cricetinae; D004249:DNA Damage / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D018014:Gene Transfer Techniques; D006801:Humans; D006822:Hybrid Cells / Q000528:radiation effects; D017404:In Situ Hybridization, Fluorescence; D051379:Mice