title: Genetic interactions between RAD51 and its paralogues for centrosome fragmentation and ploidy control, independently of the sensitivity to genotoxic stresses.
abstract: We evaluate here whether RAD51 and its paralogues XRCC2 and XRCC3 act via a common pathway for sensitivity to genotoxic stress, centrosome fragmentation and chromosome stability. We expressed the RAD51 dominant-negative SMRAD51 in irs1 and irs1SF cells, defective for XRCC2 and XRCC3, respectively, and in their corresponding wild-type cells (V79 and AA8, respectively). V79-SMRAD51 cells are sensitive to mitomycin C (MMC), but SMRAD51 did not further sensitize irs1 cells to MMC, showing that SMRAD51 and XRCC2 act on the same pathway for resistance to MMC. However, in contrast to irs1 and irs1SF cells, SMRAD51-V79 and SMRAD51-AA8 cells are not sensitive to gamma-rays or UV-C. Despite these differences in sensitivity, SMRAD51-expressing cells and xrcc2- or xrcc3-defective cells show similar increased levels of centrosome fragmentation. This spontaneous centrosome fragmentation is resistant to caffeine, suggesting that ATM and ATR are not involved. Consistent with centrosome fragmentation, increased aneuploidy was measured in irs1 and SMRAD51-expressing cells. Expression of SMRAD51 in irs1 or irs1SF cells did not increase further the frequency of multipolar cells. Thus, RAD51, XRCC2 and XRCC3 act in the same pathway for centrosome fragmentation, independently of the sensitivity to exogenous genotoxic stresses and of the ATM/ATR pathway.
authors.affiliation: UMR CNRS/CEA 217, Direction des Sciences du Vivant, Département de Radiobiologie et Radiopathologie, 18 route du Panorama, PO Box 06, Bat 05, 92265 Fontenay-aux-Roses Cedex, France.
authors.forename: Fayza
authors.initials: F
authors.lastname: Daboussi
authors.forename: John
authors.initials: J
authors.lastname: Thacker
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Lopez
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002460:Cell Line; D018385:Centrosome / Q000187:drug effects / Q000473:pathology*; D006224:Cricetinae; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D016685:Mitomycin / Q000009:adverse effects; D019384:Nucleic Acid Synthesis Inhibitors / Q000009:adverse effects; D011003:Ploidies; D051135:Rad51 Recombinase; D011839:Radiation, Ionizing; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D004268:DNA-Binding Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin; C495153:RAD51 protein, human; D051135:Rad51 Recombinase