title: Homology-directed repair is required for the development of radioresistance during S phase: interplay between double-strand break repair and checkpoint response.
abstract: The S-phase-dependent radioresistance to killing uniformly seen in eukaryotic cells is absent in radiosensitive mutants with defects in genes involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (homologous recombination repair: HRR). This implicates, for the first time, a concrete DNA repair process in the radiosensitivity of a specific cell cycle phase. The cell cycle-dependent fluctuations in radiosensitivity reflect a fundamental and well-documented radiobiological phenomenon that still awaits a detailed molecular characterization. The underlying mechanisms are likely to combine aspects of DNA repair and cell cycle regulation. Advances in both fields allow a first dissection in the cell cycle of the molecular interplay between DSB repair and DNA damage checkpoint response and its contribution to cell survival. Here we review the available literature on the topic, speculate on the ramifications of this information for our understanding of cellular responses to DNA damage, and discuss future directions in research. An effort is made to integrate relevant phenomena of radiation action, such as low-dose radiosensitivity and the G(2) assay in this scheme.
authors.affiliation: Institute of Medical Radiation Biology, University Duisburg-Essen Medical School, Essen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Tamulevicius
authors.forename: Minli
authors.initials: M
authors.lastname: Wang
authors.forename: George
authors.initials: G
authors.lastname: Iliakis
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D016196:S Phase / Q000528:radiation effects*; D013997:Time Factors
chemical_list: D002110:Caffeine