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Base-resolution analysis of deoxyuridine at genome scale based on artificial incorporation modified nucleobase

ABSTRACT: Base-resolution analysis of deoxyuridine at genome scale based on artificial incorporation modified nucleobase

PROVIDER: PRJNA595860 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10700783_1.fastq.gz	Fastqsanger.gz
	SRR10700783_2.fastq.gz	Fastqsanger.gz
	SRR10700784_1.fastq.gz	Fastqsanger.gz
	SRR10700784_2.fastq.gz	Fastqsanger.gz
	SRR11968204_1.fastq.gz	Fastqsanger.gz

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Base-resolution analysis of deoxyuridine at genome scale based on artificial incorporation modified nucleobase

Project description:Deoxyuridine (dU) in DNA can result from deamination of cytosine and dUMP misincorporation. The easy single-nucleotide resolution assay for dU are crucial to understanding its role in genome. Herein, we present a new concept of “base substitution” for accurate single-nucleotide resolution profiling of dU. The method termed AI-Seq (Artificial Incorporation of a modified nucleobase for sequencing) was developed using artificial cytosine (N3-C) to replace dU. After the artificial base construction, dU can read as cytosine during polymerase chain reaction assay. AI-seq was validated on synthetic DNA and then applied to the genome of HEK293T cell line. Collectively, the “base substitution” provides a novel approach for generating comprehensive information about the distribution of dU and can be potentially adapted to detect other epigenetic modifications.

2021-03-22 | GSE142071 | GEO

Base-Resolution Analysis of Deoxyuridine at the Genome Scale Based on the Artificial Incorporation Modified Nucleobase.

Project description:Deamination of cytosine and dUMP misincorporation have been found to be capable of producing uracil in the genome. This study presents the AI-seq (artificial incorporation modified nucleobase for sequencing), a "base substitution", which not only is capable of profiling uracil at single-nucleotide resolution and showing its centromeric enrichment but could also reveal that the identified uracil sites are derived from cytosine deamination. All the results indicate the potential biological significance of uracil as the epigenetic modification.

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Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells

Project description:MR1T cells are a recently discovered class of T cells that recognize antigens presented by the MHC-I–related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.

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