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Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.

Publication ,  Journal Article
Kim, N; Abdulovic, AL; Gealy, R; Lippert, MJ; Jinks-Robertson, S
Published in: DNA Repair (Amst)
September 1, 2007

A high level of transcription has been associated with elevated spontaneous mutation and recombination rates in eukaryotic organisms. To determine whether the transcription level is directly correlated with the degree of genomic instability, we have developed a tetracycline-regulated LYS2 reporter system to modulate the transcription level over a broad range in Saccharomyces cerevisiae. We find that spontaneous mutation rate is directly proportional to the transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es). Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions. The effect of replication fork progression was probed by comparing the mutational rates and spectra in yeast strains with the reporter gene placed in two different orientations near a well-characterized replication origin. The effect of endogenous DNA damage accumulation was investigated by studying TAM in strains defective in nucleotide excision repair or in lesion bypass by the translesion polymerase Polzeta. Our results suggest that both replication orientation and endogenous lesion accumulation play significant roles in TAM, particularly in terms of mutation spectra.

Duke Scholars

Published In

DNA Repair (Amst)

DOI

ISSN

1568-7864

Publication Date

September 1, 2007

Volume

6

Issue

9

Start / End Page

1285 / 1296

Location

Netherlands

Related Subject Headings

  • Transcription, Genetic
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Reverse Transcriptase Polymerase Chain Reaction
  • Mutation
  • Mutagenesis
  • Molecular Sequence Data
  • Genomic Instability
  • Gene Expression Regulation, Fungal
  • Developmental Biology
 

Citation

APA
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ICMJE
MLA
NLM
Kim, N., Abdulovic, A. L., Gealy, R., Lippert, M. J., & Jinks-Robertson, S. (2007). Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication. DNA Repair (Amst), 6(9), 1285–1296. https://doi.org/10.1016/j.dnarep.2007.02.023
Kim, Nayun, Amy L. Abdulovic, Regan Gealy, Malcolm J. Lippert, and Sue Jinks-Robertson. “Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.DNA Repair (Amst) 6, no. 9 (September 1, 2007): 1285–96. https://doi.org/10.1016/j.dnarep.2007.02.023.
Kim N, Abdulovic AL, Gealy R, Lippert MJ, Jinks-Robertson S. Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication. DNA Repair (Amst). 2007 Sep 1;6(9):1285–96.
Kim, Nayun, et al. “Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.DNA Repair (Amst), vol. 6, no. 9, Sept. 2007, pp. 1285–96. Pubmed, doi:10.1016/j.dnarep.2007.02.023.
Kim N, Abdulovic AL, Gealy R, Lippert MJ, Jinks-Robertson S. Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication. DNA Repair (Amst). 2007 Sep 1;6(9):1285–1296.
Journal cover image

Published In

DNA Repair (Amst)

DOI

ISSN

1568-7864

Publication Date

September 1, 2007

Volume

6

Issue

9

Start / End Page

1285 / 1296

Location

Netherlands

Related Subject Headings

  • Transcription, Genetic
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Reverse Transcriptase Polymerase Chain Reaction
  • Mutation
  • Mutagenesis
  • Molecular Sequence Data
  • Genomic Instability
  • Gene Expression Regulation, Fungal
  • Developmental Biology