Maintenance of genome stability is critical in human cells. Mutations in or loss of genome stability pathways can lead to a number of pathologies including cancer. hSSB1 is a critical DNA repair protein functioning in the repair and signalling of stalled DNA replication forks, double strand DNA breaks and oxidised DNA lesions. The BLM helicase is central to the repair of both collapsed DNA replication forks and double strand DNA breaks by homologous recombination. In this study, we demonstrate that hSSB1 and BLM helicase form a complex in cells and the interaction is altered in response to ionising radiation (IR). BLM and hSSB1 also co-localised at nuclear foci following IR-induced double strand breaks and stalled replication forks. We show that hSSB1 depleted cells contain less BLM protein and that this deficiency is due to proteasome mediated degradation of BLM. Consequently, there is a defect in recruitment of BLM to chromatin in response to ionising radiation-induced DSBs and to hydroxyurea-induced stalled and collapsed replication forks. Our data highlights that BLM helicase and hSSB1 function in a dynamic complex in cells and that this complex is likely required for BLM protein stability and function.

中文翻译：

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hSSB1与BLM解旋酶缔合并促进其稳定性。

基因组稳定性的维持对于人类细胞至关重要。基因组稳定途径的突变或丧失可导致许多疾病，包括癌症。hSSB1是一种重要的DNA修复蛋白，可在失速的DNA复制叉，双链DNA断裂和氧化的DNA损伤的修复和信号传导中起作用。BLM解旋酶是通过同源重组修复折叠的DNA复制叉和双链DNA断裂的关键。在这项研究中，我们证明了hSSB1和BLM解旋酶在细胞中形成复合物，并且其相互作用因电离辐射（IR）而改变。在IR引起的双链断裂和复制叉停滞后，BLM和hSSB1也共定位在核灶处。我们显示，hSSB1耗尽的细胞包含较少的BLM蛋白，并且这种缺陷是由于蛋白酶体介导的BLM降解。因此，响应于电离辐射诱导的DSB和羟基脲诱导的停滞和塌陷的复制叉，BLM募集到染色质中存在缺陷。我们的数据强调了BLM解旋酶和hSSB1在细胞中的动态复合物中起作用，并且该复合物可能是BLM蛋白质稳定性和功能所必需的。