ArsR Family Regulator MSMEG_6762 Mediates the Programmed Cell Death by Regulating the Expression of HNH Nuclease in Mycobacteria

ArsR家族调控因子MSMEG_6762通过调控分枝杆菌中HNH核酸酶的表达介导程序性细胞死亡

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作者:Xiangke Duan ,Xue Huang ,Junqi Xu ,Xue Li ,Jingjing Niu ,Xiaoli Du ,Xiaoyu Wang ,Jiang Li ,Michael Kelly ,Jiaohan Guo ,Ke Zhang ,Yu Huang ,Biao Kan ,Jianping Xie

Abstract

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in Mycobacterium smegmatis, an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, MSMEG_6762, leads to cell death. Transcriptome analysis revealed an increase in the genes' transcripts involved in DNA repair and homologous recombination, and in three members of HNH family DNases. Knockout of one of the DNase genes, MSMEG_1275, alleviated cell death and its over-expression of programmed cell death. Purified MSMEG_1275 cleaved the M. smegmatis DNA at multiple sites. Overall, our results indicate that the MSMEG_6762 affects cell death and is mediated, at least partially, by activation of the HNH nuclease expression under a stress condition. Keywords: ArsR family regulator; DNA damage; HNH nuclease; Mycobacterium smegmatis; programmed cell death (PCD).

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