研究动态
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人类线粒体蛋白质HSPD1结合并调节DNA中脱氧肌苷的修复。

Human Mitochondrial Protein HSPD1 Binds to and Regulates the Repair of Deoxyinosine in DNA.

发表日期:2023 Feb 28
作者: Xiaofang Zheng, Sijia Chang, Yini Liu, Xiaoxia Dai, Changjun You
来源: JOURNAL OF PROTEOME RESEARCH

摘要:

脱氧肌醇核苷(dI)在DNA中的生成是基因突变最重要的源之一,可能导致癌症和其他人类疾病。对dI生物学后果的进一步了解需要鉴定和功能特征化dI结合蛋白。在此,我们采用基于质谱的蛋白质组学方法检测可能感知DNA中dI存在的细胞蛋白。我们的研究结果表明,人线粒体热休克蛋白60(HSPD1)可以与dI载体DNA相互作用。我们进一步证明了HSPD1参与亚硝酸钠诱导的DNA损伤响应和体外以及人类细胞中dI水平调节。这些发现揭示了HSPD1作为一个新的dI结合蛋白,在人类细胞的线粒体DNA损伤控制中可能发挥重要作用。
The generation of deoxyinosine (dI) in DNA is one of the most important sources of genetic mutations, which may lead to cancer and other human diseases. A further understanding of the biological consequences of dI necessitates the identification and functional characterizations of dI-binding proteins. Herein, we employed a mass spectrometry-based proteomics approach to detect the cellular proteins that may sense the presence of dI in DNA. Our results demonstrated that human mitochondrial heat shock protein 60 (HSPD1) can interact with dI-bearing DNA. We further demonstrated the involvement of HSPD1 in the sodium nitrite-induced DNA damage response and in the modulation of dI levels in vitro and in human cells. Together, these findings revealed HSPD1 as a novel dI-binding protein that may play an important role in the mitochondrial DNA damage control in human cells.