Centriole separation in DNA damage‐induced centrosome amplification
Centriole separation in DNA damage‐induced centrosome amplification
复制标题
DNA损伤诱导的中心体扩增中的中心粒分离
DOI：
10.1002/em.20477
复制
发表时间：
2009
影响因子：
2.8
通讯作者：
C. Morrison
中科院分区：
文献类型：
--
作者：
Chiara Saladino;E. Bourke;Pauline C. Conroy;C. Morrison
改变的中心体数量在肿瘤细胞中被观察到对DNA损伤治疗的反应，并被假设有助于癌症的发展。DNA损伤后中心体和染色体周期断开的机制尚不清楚。在这里，我们表明，在缺乏DNA-PK，Ku 70，H2 AX，Xpa和Scc 1的鸡DT 40细胞中，中心体扩增在电离辐射（IR）后发生，表明这些活动不是中心体扩增所必需的。我们发现，抑制拓扑异构酶II诱导Chk 1依赖性中心体扩增，与IR后观察到的反应相似。在永生化的非转化hTERT-RPE 1系中，我们观察到中心粒分裂，随后是IR后的剂量依赖性中心体扩增。我们发现IR导致U2 OS骨肉瘤细胞中心体扩增过程中形成单个而非多个子中心粒。BRCA 1和BRCA 2突变肿瘤细胞的分析显示，在没有任何治疗的情况下，中心粒分裂水平较高。IR引起BRCA 1突变乳腺癌细胞中心体扩增的显着水平。这些数据表明，在鸡细胞、非转化的人细胞和人肿瘤细胞系中，中心体扩增发生在不同形式的DNA损伤后，表明这是对DNA损伤治疗的一般反应。总之，我们的数据表明，中心粒分裂是增强中心体扩增的关键步骤，中心体扩增是DNA损伤的一般反应。Environ.摩尔变异体2009.© 2009 Wiley利斯公司
Altered centrosome numbers are seen in tumor cells in response to DNA damaging treatments and are hypothesised to contribute to cancer development. The mechanism by which the centrosome and chromosome cycles become disconnected after DNA damage is not yet clear. Here, we show that centrosome amplification occurs after ionising radiation (IR) in chicken DT40 cells that lack DNA‐PK, Ku70, H2AX, Xpa, and Scc1, demonstrating that these activities are not required for centrosome amplification. We show that inhibition of topoisomerase II induces Chk1‐dependent centrosome amplification, a similar response to that seen after IR. In the immortalised, nontransformed hTERT‐RPE1 line, we observed centriole splitting, followed by dose‐dependent centrosome amplification, after IR. We found that IR results in the formation of single, not multiple, daughter centrioles during centrosome amplification in U2OS osteosarcoma cells. Analysis of BRCA1 and BRCA2 mutant tumor cells showed high levels of centriole splitting in the absence of any treatment. IR caused pronounced levels of centrosome amplification in BRCA1 mutant breast cancer cells. These data show that centrosome amplification occurs after different forms of DNA damage in chicken cells, in nontransformed human cells and in human tumor cell lines, indicating that this is a general response to DNA damaging treatments. Together, our data suggest that centriole splitting is a key step in potentiation of the centrosome amplification that is a general response to DNA damage. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.
DOI：
10.1073/pnas.170093297
发表时间：
2000-08-29
影响因子：
11.1
作者：
Duensing, S;Lee, LY;Münger, K
通讯作者：
Münger, K
影响因子：
11.8
作者：
Strnad, Petr;Leidel, Sebastian;Goenczy, Pierre
通讯作者：
Goenczy, Pierre