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病毒回文 DNA 序列触发的 DdmABC 依赖性死亡。

DdmABC-dependent death triggered by viral palindromic DNA sequences.

机构信息

Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

出版信息

Cell Rep. 2024 Jul 23;43(7):114450. doi: 10.1016/j.celrep.2024.114450. Epub 2024 Jul 13.

Abstract

Defense systems that recognize viruses provide important insights into both prokaryotic and eukaryotic innate immunity mechanisms. Such systems that restrict foreign DNA or trigger cell death have recently been recognized, but the molecular signals that activate many of these remain largely unknown. Here, we characterize one such system in pandemic Vibrio cholerae responsible for triggering cell density-dependent death (CDD) of cells in response to the presence of certain genetic elements. We show that the key component is the Lamassu DdmABC anti-phage/plasmid defense system. We demonstrate that signals that trigger CDD were palindromic DNA sequences in phages and plasmids that are predicted to form stem-loop hairpins from single-stranded DNA. Our results suggest that agents that damage DNA also trigger DdmABC activation and inhibit cell growth. Thus, any infectious process that results in damaged DNA, particularly during DNA replication, can in theory trigger DNA restriction and death through the DdmABC abortive infection system.

摘要

识别病毒的防御系统为原核和真核先天免疫机制提供了重要的见解。最近已经发现了限制外源 DNA 或触发细胞死亡的此类系统,但激活其中许多系统的分子信号在很大程度上仍然未知。在这里,我们描述了大流行霍乱弧菌中的这样一个系统,该系统负责触发细胞密度依赖性死亡(CDD),以响应某些遗传元件的存在。我们表明,关键组件是 Lamassu DdmABC 抗噬菌体/质粒防御系统。我们证明,触发 CDD 的信号是噬菌体和质粒中的回文 DNA 序列,这些序列预计从单链 DNA 形成茎环发夹。我们的结果表明,损伤 DNA 的试剂也会触发 DdmABC 的激活并抑制细胞生长。因此,任何导致 DNA 损伤的感染过程,特别是在 DNA 复制期间,理论上都可以通过 DdmABC 流产感染系统触发 DNA 限制和死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e20/11707656/c6ce0a079f70/nihms-2037413-f0002.jpg

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