Chapter 10 Naturally Occurring Modified Nucleosides in DNA

Ehrlich, Melanie; Zhang, Xian-Yang

doi:10.1016/s0301-4770(08)61496-7

Cited by 3 publications

(4 citation statements)

References 245 publications

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“…However, functions of 6mA in eukaryotic systems remained unclear until very recently. The lack of R-M systems suggests that 6mA mainly exerts regulatory roles in these unicellular eukaryotes (Ehrlich and Zhang, 1990). On the other hand, the existence of 6mA in higher eukaryotes, which was supported by indirect evidence, hinted that 6mA might be another potential epigenetic DNA mark in eukaryotes in addition to 5-methylcytosine (Ratel et al, 2006).…”

Section: A Brief History Of Dna 5-methylcytosine Methylation In Highementioning

confidence: 99%

Nucleic Acid Modifications in Regulation of Gene Expression

Chen

Zhao

2016

Cell Chemical Biology

236

182

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Nucleic acids carry a wide range of different chemical modifications. In contrast to previous views that these modifications are static and only play fine-tuning functions, recent research advances paint a much more dynamic picture. Nucleic acids carry diverse modifications and employ these chemical marks to exert essential or critical influences in a variety of cellular processes in eukaryotic organisms. This review covers several nucleic acid modifications that play important regulatory roles in biological systems, especially in regulation of gene expression: 5-methylcytosine (5mC) and its oxidative derivatives, and N6 -methyladenine (6mA) in DNA; N6 -methyladenosine (m6A), pseudouridine (), and 5-methylcytosine (m5C) in messenger RNA and long non-coding RNA. Modifications in other non-coding RNAs, such as tRNA, miRNA, and snRNA, are also briefly summarized. We provide brief historical perspective of the field, and highlight recent progress in identifying diverse nucleic acid modifications and exploring their functions in different organisms. Overall, we believe that work in this field will yield additional layers of both chemical and biological complexity as we continue to uncover functional consequences of known nucleic acid modifications and discover new ones.

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Section: A Brief History Of Dna 5-methylcytosine Methylation In Highementioning

confidence: 99%

Nucleic Acid Modifications in Regulation of Gene Expression

Chen

Zhao

2016

Cell Chemical Biology

236

182

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“…Although common in bacteria, no corresponding restriction endonucleases have been reported in these species. Therefore, 6mA in these unicellular eukaryotic genomes has long been suspected of possessing functions other than exclusion of foreign DNA or viruses (Ehrlich and Zhang, 1990). Additionally, evidences for the existence of 6mA in plants, insects, and mammals have also been reported.…”

Section: Introductionmentioning

confidence: 99%

N6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas

Luo

Chen

et al. 2015

Cell

461

577

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SUMMARY N6-methyldeoxyadenosine (6mA or m6A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria, and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution, and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms.

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“…It has also been shown that virus DNA itself may encode restriction-modification systems that facilitate the viral infection (23). As well as being part of restriction-modification systems, DNA methylation may also be involved in regulation of transcription, DNA replication and repair, mutation, and differentiation (1,6,7,18).Essentially all of the methylases that have been isolated methylate cytosine at the N4 or C' positions in the pyrimidine ring or adenine (A) at the N6 position in the purine ring (10). (4,14,15,24,25).…”

mentioning

confidence: 99%

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confidence: 99%

Unique modification of adenine in genomic DNA of the marine cyanobacterium Trichodesmium sp. strain NIBB 1067

et al. 1991

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The genomic DNA of the marine nonheterocystous nitrogen-fixing cyanobacterium Trichodesmium sp. strain NIBB 1067 was found to be highly resistant to DNA restriction endonucleases. The DNA was digested extensively by the restriction enzyme DpnI, which requires adenine methylation for activity. The DNA composition, determined by high-performance liquid chromatography (HPLC), was found to be 69% AT. Surprisingly, it was found that a modified adenine which was not methylated at the usual N6 position was present and made up 4.7 mol% of the nucleosides in Trichodesmium DNA (15 mol% of deoxyadenosine). In order for adenine residues to be modified at this many positions, there must be many modifying enzymes or at least one of the modifying enzymes must have a degenerate recognition site. The reason(s) for this extensive methylation has not yet been determined but may have implications for the ecological success of this microorganism in nature.The DNA of many prokaryotic and eukaryotic organisms is modified to some extent by DNA methyltransferases which methylate nucleotide bases in double-stranded genomic DNA (1). The reasons for the chemical modification of nucleotide bases in DNA are not yet fully understood, but at least in prokaryotes, modification is usually part of a restriction-modification system for defense against invasion by foreign DNA such as viruses (2). This type of enzyme modifies specific bases at recognition sites in the genomic DNA that would otherwise be cut by the cell's corresponding restriction endonuclease. In this way, the cell can destroy foreign DNA with restriction enzymes while protecting its own genomic DNA by methylating the restriction site (2). It has also been shown that virus DNA itself may encode restriction-modification systems that facilitate the viral infection (23). As well as being part of restriction-modification systems, DNA methylation may also be involved in regulation of transcription, DNA replication and repair, mutation, and differentiation (1,6,7,18).Essentially all of the methylases that have been isolated methylate cytosine at the N4 or C' positions in the pyrimidine ring or adenine (A) at the N6 position in the purine ring (10). (4,14,15,24,25). While constructing a restriction map of the nitrogenase genes from DNA isolated from pure cultures of Trichodesmium sp. strain NIBB 1067, we discovered a unique property of Trichodesmium DNA.DNA from Trichodesmium sp. strain NIBB 1067 was extracted as described previously (23), except for the addition of a 15-min precipitation (4°C) step in 1 M NaCl to eliminate polysaccharide (9). RNA was digested with DNase-free RNase. The genomic DNA was digested with restriction enzymes for 6 h or overnight (37°C). All enzymes were from New England Biolabs (Beverly, Mass.), except MaeI (Boehringer Mannheim, Indianapolis, Ind.), and digests were performed with the manufacturer's supplied or recommended buffer. Enzyme digests were performed overnight at 37°C. Lambda DNA digested with Hindlll and 4X174 DNA digested with HaeIII were used for s...

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Chapter 10 Naturally Occurring Modified Nucleosides in DNA

Cited by 3 publications

References 245 publications

Nucleic Acid Modifications in Regulation of Gene Expression

Nucleic Acid Modifications in Regulation of Gene Expression

N6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas

Unique modification of adenine in genomic DNA of the marine cyanobacterium Trichodesmium sp. strain NIBB 1067

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