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首页> 外文期刊>Journal of Cellular Physiology >Link between DNA damage and centriole disengagement/reduplication in untransformed human cells
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Link between DNA damage and centriole disengagement/reduplication in untransformed human cells

机译：DNA损伤和中心体之间的联系脱离untransformed /重复人类细胞

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摘要

The radiation and radiomimetic drugs used to treat human tumors damage DNA in both cancer cells and normal proliferating cells. Centrosome amplification after DNA damage is well established for transformed cell types but is sparsely reported and not fully understood in untransformed cells. We characterize centriole behavior after DNA damage in synchronized untransformed human cells. One hour treatment of S phase cells with the radiomimetic drug, Doxorubicin, prolongs G2 by at least 72h, though 14% of the cells eventually go through mitosis in that time. By 72h after DNA damage we observe a 52% incidence of centriole disengagement plus a 10% incidence of extra centrioles. We find that either APC/C or Plk activities can disengage centrioles after DNA damage, though they normally work in concert. All disengaged centrioles are associated with γ-tubulin and maturation markers and thus, should in principle be capable of reduplicating and organizing spindle poles. The low incidence of reduplication of disengaged centrioles during G2 is due to the p53-dependent expression of p21 and the consequent loss of Cdk2 activity. We find that 26% of the cells going through mitosis after DNA damage contain disengaged or extra centrioles. This could produce genomic instability through transient or persistent spindle multipolarity. Thus, for cancer patients the use of DNA damaging therapies raises the chances of genomic instability and evolution of transformed characteristics in proliferating normal cell populations.
机译：辐射和radiomimetic药物用于治疗人类在癌细胞和肿瘤破坏DNA正常的增殖细胞。DNA损伤后放大但建立转化细胞类型稀疏的报道并没有完全理解untransformed细胞。DNA损伤后行为同步untransformed人类细胞。S期细胞radiomimetic药物,阿霉素,延长G2至少72 h最终14%的细胞通过有丝分裂那个时候。中心体脱离加上发生率52%10%的几率额外的中心粒。APC / C或Plk活动可以解除中心粒DNA损伤后,尽管他们通常协同工作。与γ微管蛋白和成熟标记因此,原则上应能力重复和组织纺锤体两极。发病率低闲散的复本在G2是因为p53-dependent中心粒Cdk2 p21的表达和随之而来的损失活动。通过有丝分裂后DNA损伤脱离或额外的中心粒。通过瞬态或产生基因组不稳定性持久的主轴多极化。癌症患者使用DNA损害疗法提出了基因组不稳定和的机会转换特征的进化正常增殖细胞群。

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