BRCA2 是一种重要的肿瘤抑制蛋白，参与促进 DNA 损伤的忠实修复。 BRCA2 的活性需要精确调节，以便在需要的时间和地点发挥作用。在这里，我们使用像差校正多焦点显微镜 (acMFM) 量化了活细胞中 BRCA2 的时空动态。使用多色成像来识别 DNA 损伤位点，我们能够量化其在细胞核和 DNA 损伤位点的动态运动模式。虽然位于 DNA 损伤位点附近的大部分 BRCA2 分子看起来是不动的，但另外一部分分子表现出亚扩散运动，这提供了一种在 DNA 损伤处保留更多分子的潜在机制。超分辨率显微镜揭示了 BRCA2 相对于其他 DNA 修复因子在 DNA 损伤位点的定位不均匀。这表明 DNA 损伤周围的染色质中存在多个纳米级区室，这可能在 BRCA2 对修复过程调节的贡献中发挥重要作用。© 作者 2024。由牛津大学出版社代表出版核酸研究。

BRCA2 is an essential tumor suppressor protein involved in promoting faithful repair of DNA lesions. The activity of BRCA2 needs to be tuned precisely to be active when and where it is needed. Here, we quantified the spatio-temporal dynamics of BRCA2 in living cells using aberration-corrected multifocal microscopy (acMFM). Using multicolor imaging to identify DNA damage sites, we were able to quantify its dynamic motion patterns in the nucleus and at DNA damage sites. While a large fraction of BRCA2 molecules localized near DNA damage sites appear immobile, an additional fraction of molecules exhibits subdiffusive motion, providing a potential mechanism to retain an increased number of molecules at DNA lesions. Super-resolution microscopy revealed inhomogeneous localization of BRCA2 relative to other DNA repair factors at sites of DNA damage. This suggests the presence of multiple nanoscale compartments in the chromatin surrounding the DNA lesion, which could play an important role in the contribution of BRCA2 to the regulation of the repair process.© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.