The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA

Non-canonical residue in DNA is a major and conserved source of genome instability. The appearance of uracil residues in DNA accompanies a significant mutagenic consequence and is regulated at multiple levels, from the concentration of available dUTP in the nucleotide pool to the excision repair for...

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Main Authors: Stokdyk, Kasey, Kim, Nayun, Owiti, Norah Auma
其他作者: Massachusetts Institute of Technology. Department of Biological Engineering
格式: 文件
语言:English
出版: Springer Berlin Heidelberg 2018
在线阅读:http://hdl.handle.net/1721.1/118832
https://orcid.org/0000-0002-5061-7434
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author Stokdyk, Kasey
Kim, Nayun
Owiti, Norah Auma
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Stokdyk, Kasey
Kim, Nayun
Owiti, Norah Auma
author_sort Stokdyk, Kasey
collection MIT
description Non-canonical residue in DNA is a major and conserved source of genome instability. The appearance of uracil residues in DNA accompanies a significant mutagenic consequence and is regulated at multiple levels, from the concentration of available dUTP in the nucleotide pool to the excision repair for removal from DNA. Recently, an interesting phenomenon of transcription-associated elevation in uracil-derived mutations was described in Saccharomyces cerevisiae genome. While trying to understand the variability in mutagenesis, we uncovered that the frequency of uracil incorporation into DNA can vary depending on the transcription rate and that the non-replicative, repair-associated DNA synthesis underlies the higher uracil density of the actively transcribed genomic loci. This novel mechanism brings together the chemical vulnerability of DNA under transcription and the uracil-associated mutagenesis, and has the potential to apply to other non-canonical residues of mutagenic importance. Keyword: DNA repair; Non-canonical nucleotides; Transcription-associated mutagenesis; Uracil dUTPase
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spelling mit-1721.1/1188322022-09-30T13:37:29Z The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA Stokdyk, Kasey Kim, Nayun Owiti, Norah Auma Massachusetts Institute of Technology. Department of Biological Engineering Owiti, Norah Auma Non-canonical residue in DNA is a major and conserved source of genome instability. The appearance of uracil residues in DNA accompanies a significant mutagenic consequence and is regulated at multiple levels, from the concentration of available dUTP in the nucleotide pool to the excision repair for removal from DNA. Recently, an interesting phenomenon of transcription-associated elevation in uracil-derived mutations was described in Saccharomyces cerevisiae genome. While trying to understand the variability in mutagenesis, we uncovered that the frequency of uracil incorporation into DNA can vary depending on the transcription rate and that the non-replicative, repair-associated DNA synthesis underlies the higher uracil density of the actively transcribed genomic loci. This novel mechanism brings together the chemical vulnerability of DNA under transcription and the uracil-associated mutagenesis, and has the potential to apply to other non-canonical residues of mutagenic importance. Keyword: DNA repair; Non-canonical nucleotides; Transcription-associated mutagenesis; Uracil dUTPase 2018-10-31T19:52:35Z 2018-10-31T19:52:35Z 2018-10 2018-10 2018-10-18T04:01:35Z Article http://purl.org/eprint/type/JournalArticle 0172-8083 1432-0983 http://hdl.handle.net/1721.1/118832 Owiti, Norah et al. “The Etiology of Uracil Residues in the Saccharomyces Cerevisiae Genomic DNA.” Current Genetics (October 2018): 1-7 © 2018 The Author(s) https://orcid.org/0000-0002-5061-7434 en https://doi.org/10.1007/s00294-018-0895-8 Current Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf Springer Berlin Heidelberg Springer Berlin Heidelberg
spellingShingle Stokdyk, Kasey
Kim, Nayun
Owiti, Norah Auma
The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA
title The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA
title_full The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA
title_fullStr The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA
title_full_unstemmed The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA
title_short The etiology of uracil residues in the Saccharomyces cerevisiae genomic DNA
title_sort etiology of uracil residues in the saccharomyces cerevisiae genomic dna
url http://hdl.handle.net/1721.1/118832
https://orcid.org/0000-0002-5061-7434
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