Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Laboratory of Biochemical Cell Dynamics, Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Commun Biol. 2023 Oct 13;6(1):1038. doi: 10.1038/s42003-023-05406-9.
The Schlafen (SLFN)11 gene has been implicated in various biological processes such as suppression of HIV replication, replication stress response, and sensitization of cancer cells to chemotherapy. Due to the rapid diversification of the SLFN family members, it remains uncertain whether a direct ortholog of human SLFN11 exists in mice. Here we show that mSLFN8/9 and hSLFN11 were rapidly recruited to microlaser-irradiated DNA damage tracks. Furthermore, Slfn8/9 expression could complement SLFN11 loss in human SLFN11 cells, and as a result, reduced the growth rate to wild-type levels and partially restored sensitivity to DNA-damaging agents. In addition, both Slfn8/9 and SLFN11 expression accelerated stalled fork degradation and decreased RPA and RAD51 foci numbers after DNA damage. Based on these results, we propose that mouse Slfn8 and Slfn9 genes may share an orthologous function with human SLFN11. This notion may facilitate understanding of SLFN11's biological role through in vivo studies via mouse modeling.
Schlafen (SLFN)11 基因参与多种生物学过程，如抑制 HIV 复制、复制应激反应以及增强癌细胞对化疗的敏感性。由于 SLFN 家族成员的快速多样化，目前尚不确定在小鼠中是否存在人类 SLFN11 的直接直系同源物。在这里，我们表明 mSLFN8/9 和 hSLFN11 被迅速募集到微激光照射的 DNA 损伤轨迹中。此外，Slfn8/9 的表达可以弥补人 SLFN11 细胞中 SLFN11 的缺失，从而降低生长速度至野生型水平，并部分恢复对 DNA 损伤剂的敏感性。此外，Slfn8/9 和 SLFN11 的表达均加速了停滞叉的降解，并减少了 DNA 损伤后 RPA 和 RAD51 焦点的数量。基于这些结果，我们提出小鼠 Slfn8 和 Slfn9 基因可能与人 SLFN11 具有同源功能。这一概念可能通过小鼠模型的体内研究促进对 SLFN11 生物学作用的理解。
