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Importance of the tmRNA system for cell survival when transcription is blocked by DNA-protein cross-links.

Publication ,  Journal Article
Kuo, HK; Krasich, R; Bhagwat, AS; Kreuzer, KN
Published in: Mol Microbiol
November 2010

Anticancer drug 5-azacytidine (aza-C) induces DNA-protein cross-links (DPCs) between cytosine methyltransferase and DNA as the drug inhibits methylation. We found that mutants defective in the tmRNA translational quality control system are hypersensitive to aza-C. Hypersensitivity requires expression of active methyltransferase, indicating the importance of DPC formation. Furthermore, the tmRNA pathway is activated upon aza-C treatment in cells expressing methyltransferase, resulting in increased levels of SsrA tagged proteins. These results argue that the tmRNA pathway clears stalled ribosome-mRNA complexes generated after transcriptional blockage by aza-C-induced DPCs. In support, an ssrA mutant is also hypersensitive to streptolydigin, which blocks RNA polymerase elongation by a different mechanism. The tmRNA pathway is thought to act only on ribosomes containing a 3' RNA end near the A site, and the known pathway for releasing RNA 3' ends from a blocked polymerase involves Mfd helicase. However, an mfd knockout mutant is not hypersensitive to either aza-C-induced DPC formation or streptolydigin, indicating that Mfd is not involved. Transcription termination factor Rho is also likely not involved, because the Rho-specific inhibitor bicyclomycin failed to show synergism with either aza-C or streptolydigin. Based on these findings, we discuss models for how E. coli processes transcription/translation complexes blocked at DPCs.

Duke Scholars

Published In

Mol Microbiol

DOI

EISSN

1365-2958

Publication Date

November 2010

Volume

78

Issue

3

Start / End Page

686 / 700

Location

England

Related Subject Headings

  • Transcription, Genetic
  • RNA, Bacterial
  • Protein Biosynthesis
  • Microbiology
  • Microbial Viability
  • Escherichia coli Proteins
  • Escherichia coli
  • DNA, Bacterial
  • Cross-Linking Reagents
  • Azacitidine
 

Citation

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MLA
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Kuo, H. K., Krasich, R., Bhagwat, A. S., & Kreuzer, K. N. (2010). Importance of the tmRNA system for cell survival when transcription is blocked by DNA-protein cross-links. Mol Microbiol, 78(3), 686–700. https://doi.org/10.1111/j.1365-2958.2010.07355.x
Kuo, H Kenny, Rachel Krasich, Ashok S. Bhagwat, and Kenneth N. Kreuzer. “Importance of the tmRNA system for cell survival when transcription is blocked by DNA-protein cross-links.Mol Microbiol 78, no. 3 (November 2010): 686–700. https://doi.org/10.1111/j.1365-2958.2010.07355.x.
Kuo HK, Krasich R, Bhagwat AS, Kreuzer KN. Importance of the tmRNA system for cell survival when transcription is blocked by DNA-protein cross-links. Mol Microbiol. 2010 Nov;78(3):686–700.
Kuo, H. Kenny, et al. “Importance of the tmRNA system for cell survival when transcription is blocked by DNA-protein cross-links.Mol Microbiol, vol. 78, no. 3, Nov. 2010, pp. 686–700. Pubmed, doi:10.1111/j.1365-2958.2010.07355.x.
Kuo HK, Krasich R, Bhagwat AS, Kreuzer KN. Importance of the tmRNA system for cell survival when transcription is blocked by DNA-protein cross-links. Mol Microbiol. 2010 Nov;78(3):686–700.
Journal cover image

Published In

Mol Microbiol

DOI

EISSN

1365-2958

Publication Date

November 2010

Volume

78

Issue

3

Start / End Page

686 / 700

Location

England

Related Subject Headings

  • Transcription, Genetic
  • RNA, Bacterial
  • Protein Biosynthesis
  • Microbiology
  • Microbial Viability
  • Escherichia coli Proteins
  • Escherichia coli
  • DNA, Bacterial
  • Cross-Linking Reagents
  • Azacitidine