Medical Research Council, Radiation & Genome Stability Unit, Oxon OX11 0RD, UK.
Exp Cell Res. 2011 May 1;317(8):1203-13. doi: 10.1016/j.yexcr.2011.01.021. Epub 2011 Jan 27.
In response to DNA damage, cells need robust repair mechanisms to complete the cell cycle successfully. Severe forms of DNA damage are repaired by homologous recombination (HR), in which the XRCC2 protein plays a vital role. Cells deficient in XRCC2 also show disruption of the centrosome, a key component of the mitotic apparatus. We find that this centrosome disruption is dynamic and when it occurs during mitosis it is linked directly to the onset of mitotic catastrophe in a significant fraction of the XRCC2-deficient cells. However, we also show for the first time that XRCC2 and other HR proteins, including the key recombinase RAD51, co-localize with the centrosome. Co-localization is maintained throughout the cell cycle, except when cells are finishing mitosis when RAD51 accumulates in the midbody between the separating cells. Taken together, these data suggest a tight functional linkage between the centrosome and HR proteins, potentially to coordinate the deployment of a DNA damage response at vulnerable phases of the cell cycle.
针对 DNA 损伤，细胞需要强大的修复机制才能成功完成细胞周期。严重的 DNA 损伤通过同源重组 (HR) 修复，XRCC2 蛋白在其中起着至关重要的作用。XRCC2 缺陷的细胞也显示出中心体的破坏，中心体是有丝分裂装置的关键组成部分。我们发现这种中心体的破坏是动态的，当它发生在有丝分裂过程中时，它与相当一部分 XRCC2 缺陷细胞中有丝分裂灾难的开始直接相关。然而，我们也首次表明，XRCC2 和其他 HR 蛋白，包括关键的重组酶 RAD51，与中心体共定位。共定位贯穿整个细胞周期，但当细胞完成有丝分裂时，RAD51 在分离细胞之间的中间体内积累。总之，这些数据表明中心体和 HR 蛋白之间存在紧密的功能联系，可能是为了协调细胞周期脆弱阶段的 DNA 损伤反应的部署。
