Metastasis suppressor NME1 promotes non-homologous end joining of DNA double-strand breaks
Metastasis suppressor NME1 promotes non-homologous end joining of DNA double-strand breaks
复制标题
转移抑制因子 NME1 促进 DNA 双链断裂的非同源末端连接
DOI：
10.1016/j.dnarep.2019.03.003
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发表时间：
2019-05-01
期刊：
影响因子：
3.8
通讯作者：
Pei, Huadong
中科院分区：
文献类型：
--
作者：
Xue, Renyu;Peng, Yihan;Pei, Huadong
NME1（也称为NM23-H1）是第一个被发现的肿瘤转移抑制因子，据报道其与基因组稳定性维持和癌症有关。然而，其潜在机制仍未完全了解。我们发现NME1在DNA双链断裂（dsb）的非同源末端连接（NHEJ）中是必需的。在机制上，NME1以依赖于ku - xrcc4的方式重新定位到DNA损伤位点，并调节下游LIG4的招募和末端连接效率。此外，我们发现NME1的3‘-5’外切酶活性对其在NHEJ中的功能至关重要。综上所述，我们的研究结果确定了NME1是一种新的NHEJ因子，并揭示了这种转移抑制因子如何促进基因组稳定性。
NME1 (also known as NM23-H1) was the first identified tumor metastasis suppressor, which has been reported to link with genomic stability maintenance and cancer. However its underlying mechanisms are still not fully understood. Here we find that NME1 is required for non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Mechanistically, NME1 re-localizes to DNA damage sites in a Ku-XRCC4-dependent manner, and regulates downstream LIG4 recruitment and end joining efficiency. Furthermore, we show that the 3'-5' exonuclease activity of NME1 is critical for its function in NHEJ. Taken together, our findings identify NME1 as a novel NHEJ factor, and reveal how this metastasis suppressor promotes genome stability.