RMI1的敲低会损害DNA复制应激下的DNA修复。

Knockdown of RMI1 impairs DNA repair under DNA replication stress.

作者信息

Xu Chang, Fang Lianying, Kong Yangyang, Xiao Changyan, Yang Mengmeng, Du Li-Qing, Liu Qiang

机构信息

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, NanKai University, Tianjin, China.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

出版信息

Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):158-164. doi: 10.1016/j.bbrc.2017.10.062. Epub 2017 Oct 14.

DOI:10.1016/j.bbrc.2017.10.062

PMID:29042194

Abstract

RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex with BLM, Topo IIIα, and RMI2, and its absence causes genome instability. It has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIα in response to replication stress, and that RMI1 functions downstream of BLM in promoting replication elongation. However, the precise functions of RMI1 during replication stress are not completely understood. Here we report that RMI1 knockdown cells are hypersensitive to hydroxyurea (HU). Using comet assay, we show that RMI1 knockdown cells exhibit accumulation of broken DNAs after being released from HU treatment. Moreover, we demonstrate that RMI1 facilitates the recovery from activated checkpoint and resuming the cell cycle after replicative stress. Surprisingly, loss of RMI1 results in a failure of RAD51 loading onto DNA damage sites. These findings reveal the importance of RMI1 in response to replication stress, which could explain the molecular basis for its function in maintaining genome integrity.

摘要

RMI1（RecQ介导的基因组不稳定蛋白1）与BLM、拓扑异构酶IIIα和RMI2形成保守的BTR复合物，其缺失会导致基因组不稳定。研究表明，RMI1在复制应激反应中与BLM和拓扑异构酶IIIα定位于核灶，并且RMI1在促进复制延伸方面在BLM下游发挥作用。然而，RMI1在复制应激期间的确切功能尚未完全了解。在此我们报告，RMI1敲低的细胞对羟基脲（HU）高度敏感。使用彗星试验，我们表明RMI1敲低的细胞在从HU处理中释放后表现出断裂DNA的积累。此外，我们证明RMI1促进从激活的检查点恢复并在复制应激后恢复细胞周期。令人惊讶的是，RMI1的缺失导致RAD51无法加载到DNA损伤位点。这些发现揭示了RMI1在应对复制应激中的重要性，这可以解释其在维持基因组完整性方面功能的分子基础。