Genetic interactions between RAD51 and its paralogues for centrosome fragmentation and ploidy control, independently of the sensitivity to genotoxic stresses

被引:30
作者
Daboussi, F
Thacker, J
Lopez, BS
机构
[1] CEA, CNRS, UMR 217, Direct Sci Vivant,Dept Radiobiol & Radiopathol, F-92265 Fontenay Aux Roses, France
[2] MRC, Radiat & Genome Stabil Unit, Harwell OX11 0RD, Oxon, England
关键词
RAD51; paralogues; centrosome; genotoxic stress; homologous recombination;
D O I
10.1038/sj.onc.1208438
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 c-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.
引用
收藏
页码:3691 / 3696
页数:6
相关论文
共 36 条
  • [31] Homologous recombination induced by replication inhibition, is stimulated by expression of mutant p53
    Saintigny, Y
    Lopez, BS
    [J]. ONCOGENE, 2002, 21 (03) : 488 - 492
  • [32] Characterization of homologous recombination induced by replication inhibition in mammalian cells
    Saintigny, Y
    Delacôte, F
    Varès, G
    Petitot, F
    Lambert, S
    Averbeck, D
    Lopez, BS
    [J]. EMBO JOURNAL, 2001, 20 (14) : 3861 - 3870
  • [33] Sarkaria JN, 1999, CANCER RES, V59, P4375
  • [34] Yeast Rad55 and Rad57 proteins form a heterodimer that functions with replication protein a to promote DNA strand exchange by Rad51 recombinase
    Sung, P
    [J]. GENES & DEVELOPMENT, 1997, 11 (09) : 1111 - 1121
  • [35] A surfeit of RAD51-like genes?
    Thacker, J
    [J]. TRENDS IN GENETICS, 1999, 15 (05) : 166 - 168
  • [36] Caffeine inhibits homology-directed repair of I-SceI-induced DNA double-strand breaks
    Wang, HC
    Boecker, W
    Wang, HY
    Wang, X
    Guan, J
    Thompson, LH
    Nickoloff, JA
    Iliakis, G
    [J]. ONCOGENE, 2004, 23 (03) : 824 - 834