title: Reduced apoptotic response to camptothecin in CHO cells deficient in XRCC3.
abstract: Eukaryotic cells respond to DNA damage by activation of DNA repair, cell-cycle arrest and apoptosis. Several reports suggest that such responses may be coordinated by communication between damage repair proteins and proteins signalling other cellular responses. The Rad51-guided homologous recombination (HR) repair plays an important role in recognition and repair of DNA double-strand breaks (DSBs) and cells deficient in this repair pathway become hypersensitive to agents that induce DSBs. In the work reported here we investigated the possible role of the Rad51-like HR proteins XRCC2, XRCC3 and Rad51C in apoptosis following the induction of DSBs by camptothecin. We show that a hamster cell line (irs1SF) deficient in the HR repair gene XRCC3 exhibits altered death and cell-cycle checkpoint responses following treatment with growth inhibitory concentrations of camptothecin. In contrast, hamster cells defective in XRCC2 (irs1) or Rad51C (irs3) treated with equally toxic doses of this agent exhibit a rapid induction of apoptosis similar to that seen in the parental cell line or mutant cells corrected for the HR defect. These results suggest that XRCC3 activity may be necessary for efficient entry into apoptosis in response to DSBs.
authors.affiliation: Institute for Cancer Studies, University of Sheffield School of Medicine, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: John M
authors.initials: JM
authors.lastname: Hinz
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
authors.forename: Mark
authors.initials: M
authors.lastname: Meuth
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D002166:Camptothecin / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; D002166:Camptothecin