title: Ionizing radiation-induced Rad51 nuclear focus formation is cell cycle-regulated and defective in both ATM(-/-) and c-Abl(-/-) cells.
abstract: In eukaryotes, DNA double-strand breaks (DSBs) can be repaired by either non-homologous end-joining (NHEJ) or homologous recombination (HR) pathways. Rad50 protein is a component of the Rad50/NBS1/Mre11 nuclease complex that functions in both the NHEJ and recombinational repair of DNA DSBs. On the other hand, Rad51 protein, a homolog of bacterial RecA and a member of the Rad52 epistasis group, plays a crucial role exclusively in the recombinational repair pathway. We analyzed the effects of cell cycle progression and genetic background on the ionizing radiation (IR)-induced Rad51 and Rad50 repair focus formation. Herein, we demonstrated that IR-induced Rad51, but not Rad50, nuclear focus formation was cell cycle-dependent. Furthermore, IR-induced Rad51 focus formation was defective in AT and c-Abl(-/-) cells, but not wild type or NBS cells. A decreased and delayed formation of Rad51 foci-containing nuclei was observed in AT cells upon IR, whereas in c-Abl(-/-) cells a decreased but not delayed formation of Rad51 foci-containing nuclei was observed. In conclusion, effective and prompt IR-induced Rad51 focus formation is cell cycle-regulated and requires both ATM and c-Abl.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, ROC. yuanssf@ms33.hinet.net
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
authors.forename: Hsueh-Ling
authors.initials: HL
authors.lastname: Chang
authors.forename: Eva Y-H P
authors.initials: EY
authors.lastname: Lee
mesh_terms: D017766:Acid Anhydride Hydrolases; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D019457:Chromosome Breakage; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics*; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000235:genetics*; D051135:Rad51 Recombinase; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D016315:Proto-Oncogene Proteins c-abl; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes