DNA adenine hypomethylation leads to metabolic rewiring in Deinococcus radiodurans

Shaiwale, Nayana S.; Basu, Bhakti; Deobagkar, Deepti D.; Deobagkar, Dileep N.; Apte, Shree Kumar

doi:10.1016/j.jprot.2015.05.036

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…The comparative analysis suggested that MTases encoded by ORF2230P, ORF14075P and ORF15360P are involved in 6mA modification in D. radiodurans , whereas only the MTase encoded by ORF16000P was implicated in 4mC methylation. And the protein encoded by ORF10260P ( DR_0643 ) was annotated as an RsmD-like RNA methyltransferase, which was once proposed to be a 6mA DNA MTase (Shaiwale et al, 2015). As a member of the Mme I family, DraRI in Deinococcus was reported to possess no DNA methyltransferase activity in vivo , but displayed endonuclease activity once disrupted ORF was corrected (Morgan et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the long-held assumption that D. radiodurans DNA was methyl-deficient due to the unidentified methylated bases or undetectable DNA MTase activity (Ferrandi et al, 2019), the genomic DNA (gDNA) of D. radiodurans was reported to contain 6mA and 5mC modifications (Prasad et al, 2005; Patil et al, 2017). The hypomethylation of 6mA leads to dysregulation of metabolic pathways (Shaiwale et al, 2015), whereas 5mC could regulate protein homeostasis in this bacterium (Patil et al, 2017). However, recent experiments using dot-blot and enzyme-linked apta-sorbent assays revealed the absence of 5mC modifications in the gDNA of D. radiodurans (Ferrandi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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N4-Cytosine DNA Methylation Is Involved in the Maintenance of Genomic Stability in Deinococcus radiodurans

Cai

et al. 2019

Front. Microbiol.

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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 methylome of this bacterium remain unclear. Here, we demonstrate that N 4 -cytosine is the major methylated form (4mC) in D. radiodurans . A novel methylated motif, “C 4m CGCGG” was identified that was fully attributed to M.DraR1 methyltransferase. M.DraR1 can specifically bind and methylate the second cytosine at N 4 atom of “CCGCGG” motif, preventing its digestion by a cognate restriction endonuclease. Cells deficient in 4mC modification displayed higher spontaneous rifampin mutation frequency and enhanced DNA recombination and transformation efficiency. And genes involved in the maintenance of genomic stability were differentially expressed in conjunction with the loss of M.DraR1. This study provides evidence that N 4 -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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N4-Cytosine DNA Methylation Is Involved in the Maintenance of Genomic Stability in Deinococcus radiodurans

Cai

et al. 2019

Front. Microbiol.

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“…Because both of these programs were trained using E. coli sequences with GATC m6A modifications, these results were not surprising. It has been reported that Gramnegative bacterial genomes have a relatively consistent methylation pattern of m6A for GATC positions through various growth phases and after exposure to antibiotics (Shaiwale et al, 2015;Cohen et al, 2016;Westphal et al, 2016;Liu et al, 2020). Additionally, not all GATC positions are methylated, with some being heritably nonmethylated (Blyn et al, 1990;Casadesús and Low, 2006).…”

Section: Mapping and Quality Of Long-readsmentioning

confidence: 99%

“…Such modifications have the potential to persist for generations as heritable changes (i.e., epigenetics). In bacteria, DNA methylation is also present, regulating gene expression and guiding both stress response and DNA repair (Blyn et al, 1990;Casadesús and Low, 2006;Fang et al, 2012;Beaulaurier et al, 2015;Shaiwale et al, 2015;Blow et al, 2016;Cohen et al, 2016;Westphal et al, 2016;Nye et al, 2019). Although eukaryotic and bacterial genomes may contain multiple DNA methyltransferases (MTases), each with a different substrate specification for methylation of a variety of nucleic acid substrates, the two more widely studied modifications to DNA are to cytosines, C-5 methylation (m5C) and adenosines, methylation of the N-6 (m6A or 6 mA) (Casadesús and Low, 2006;Fang et al, 2012;Blow et al, 2016;Liu et al, 2019aLiu et al, , 2019b.…”

Section: Introductionmentioning

confidence: 99%

Long-read sequencing reveals increased occurrence of genomic variants and adenosine methylation in Bacillus pumilus SAFR-032 after long-duration flight exposure onboard the International Space Station

Waters

Ledford

Wacker

et al. 2021

International Journal of Astrobiology

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Bacillus pumilus SAFR-032, an endospore-forming bacterial strain, was investigated to determine its methylation pattern (methylome) change, compared to ground control, after direct exposure to space conditions onboard the International Space Station (ISS) for 1.5 years. The resulting ISS-flown and non-flown strains were sequenced using the Nanopore MinION and an in-house method and pipeline to identify methylated positions in the genome. Our analysis indicated genomic variants and m6A methylation increased in the ISS-flown SAFR-032. To complement the broader omics investigation and explore phenotypic changes, ISS-flown and non-flown strains were compared in a series of laboratory-based chamber experiments using an X-ray irradiation source (doses applied at 250, 500, 750, 1000 and 1250 Gy); results show a potentially higher survival fraction of ISS-flown DS2 at the two highest exposures. Taken together, results from this study document lasting changes to the genome by methylation, potentially triggered by conditions in spaceflight, with functional consequences for the resistance of bacteria to stressors expected on long-duration missions beyond low Earth orbit.

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Epigenetics with special reference to the human X chromosome inactivation and the enigma of Drosophila DNA methylation

Deobagkar

2018

J Genet

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Epigenetics confers adaptability and survival advantage to an organism. Most epigenetic processes demonstrate memory and heritability. DNA methylation is an epigenetic process that adds imprints which can be inherited during cell division and across generations. DNA methylation adds an additional level of information to the basic DNA sequence and can influence chromatin organization and the function of the DNA sequence. In bacteria, it works as a defence strategy and preserves genome integrity. DNA methylation in eukaryotes has been implicated in a large number of cellular regulatory processes and is implied in development, differentiation, life style diseases and cancer. Mammals have an intricate DNA methylation machinery with dNMT1, 3A and 3B enzymes. The human X chromosome inactivation, an example of differential regulation of homologous chromosomes, is known to involve many epigenetic processes with intricate interactions of lncRNAs, miRNAs and DNA methylation. possesses very low levels of DNA methylation with only gene. Since is an important model organism for study of development and differentiation, the implications of this sparse DNA methylation and the lack of DNA methylation machinery in is discussed.

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DNA adenine hypomethylation leads to metabolic rewiring in Deinococcus radiodurans

Cited by 7 publications

References 37 publications

N4-Cytosine DNA Methylation Is Involved in the Maintenance of Genomic Stability in Deinococcus radiodurans

N4-Cytosine DNA Methylation Is Involved in the Maintenance of Genomic Stability in Deinococcus radiodurans

Long-read sequencing reveals increased occurrence of genomic variants and adenosine methylation in Bacillus pumilus SAFR-032 after long-duration flight exposure onboard the International Space Station

Epigenetics with special reference to the human X chromosome inactivation and the enigma of Drosophila DNA methylation

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