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Front. Microbiol. | doi: 10.3389/fmicb.2019.01905

N4-cytosine DNA methylation is involved in the maintenance of genomic stability in Deinococcus radiodurans

 Yuejin Hua1*,  Shengjie Li2, Jianling Cai2, Huizhi Lu2, Shuyu Mao2, Shang Dai2, Jing Hu2,  Liangyan Wang2,  Xiaoting Hua2, 3, Hong Xu2,  Bing Tian2 and  Ye Zhao2
  • 1Institute of Nuclear-Agricultural Sciences, Zhejiang University, China
  • 2Institute of Nuclear-Agricultural Sciences, Zhejiang University, China
  • 3Department of Infectious Diseases, Sir Run Run Shaw Hospital, China

DNA methylation serves as a vital component of restriction-modification (R-M) systems in bacteria, where it plays a crucial role in defense against foreign DNA. Recent studies revealed that DNA methylation has a global impact on gene expression. Deinococcus radiodurans, an ideal model organism for studying DNA repair and genomic stability, possesses unparalleled resistance to DNA-damaging agents such as irradiation and strong oxidation. However, details on the methylomes of this bacterium remain unclear. Here, we demonstrate that N4-cytosine is the major methylated form (4mC) in D. radiodurans. A novel methylated motif, ‘C4mCGCGG’ was identified that was fully attributed to M.DraR1 methyltransferase. M.DraR1 can specifically bind and methylate the second cytosine at N4 atom of ‘CCGCGG’ motif, preventing its digestion by a cognate restriction endonuclease. Importantly, cells deficient in 4mC modifications displayed higher spontaneous mutation frequency and enhanced DNA recombination and transformation efficiency. Moreover, genes involved in the maintenance of genomic stability were differentially expressed in conjunction with the loss of M.DraR1. This study provides evidence that N4-cytosine DNA methylation contributes to genomic stability of D. radiodurans and lays the foundation for further research on the mechanisms of epigenetic regulation by R-M systems in bacteria.

Keywords: Deinococcus radiodurans, genomic stability, DNA Methylation, M.DraR1 methyltransferase, Differential expression genes

Received: 01 May 2019; Accepted: 05 Aug 2019.

Copyright: © 2019 Hua, Li, Cai, Lu, Mao, Dai, Hu, Wang, Hua, Xu, Tian and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yuejin Hua, Zhejiang University, Institute of Nuclear-Agricultural Sciences, Hangzhou, China, yjhua@zju.edu.cn