BCL10 is recruited to sites of DNA damage to facilitate DNA double-strand break repair

Recent studies have found BCL10 can localize to the nucleus and that this is linked to tumor aggression and poorer prognosis. These studies suggest that BCL10 localization plays a novel role in the nucleus that may contribute to cellular transformation and carcinogenesis. In this study, we show that BCL10 functions as part of the DNA damage response (DDR). We found that BCL10 facilitates the rapid recruitment of RPA, BRCA1 and RAD51 to sites of DNA damage. Furthermore, we also found that ATM phosphorylates BCL10 in response to DNA damage. Functionally, BCL10 promoted DNA double-strand breaks repair, enhancing cell survival after DNA damage. Taken together our results suggest a novel role for BCL10 in the repair of DNA lesions.

已有研究证实，B细胞淋巴瘤/白血病10（BCL10）可定位于细胞核，且该定位特征与肿瘤侵袭性增强及不良预后显著相关。上述研究提示，BCL10在细胞核内具备全新功能，可能参与细胞转化与癌变过程。本研究表明，BCL10作为DNA损伤反应（DNA damage response, DDR）的组分发挥生物学功能。研究发现，BCL10能够促进RPA、BRCA1及RAD51快速招募至DNA损伤位点。进一步研究显示，在DNA损伤应激条件下，毛细血管扩张性共济失调突变激酶（ATM）可对BCL10进行磷酸化修饰。功能实验结果表明，BCL10可促进DNA双链断裂修复，提升细胞在DNA损伤后的存活能力。综上，本研究结果揭示了BCL10在DNA损伤修复中的全新作用。