Potential roles for DNA replication and repair functions in cell killing by streptomycin

Mir Humayun, Vasudevan Ayyappan

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The aminoglycoside streptomycin binds to ribosomes to promote mistranslation and eventual inhibition of translation. Streptomycin kills bacteria, whereas many other non-aminoglycoside inhibitors of translation do not. Because mistranslation is now known to affect DNA replication, we asked if hydroxyurea, a specific inhibitor of DNA synthesis, affects killing, and find that hydroxyurea significantly attenuates killing by streptomycin. We find that the hydroxyl radical scavengers d-mannitol and thiourea have either no effect or only a modest protective effect. The iron chelator 2,2'-dipyridyl eliminated killing by streptomycin, but further investigation revealed that it blocks streptomycin uptake. Prior treatment of cells with low-levels of methyl methanesulfonate to induce the adaptive response to alkylation leads to a significant attenuation of killing, which, together with the hydroxyurea effect, suggests roles for DNA replication and repair functions in cell killing by streptomycin.

Original languageEnglish (US)
Pages (from-to)87-91
Number of pages5
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume749
Issue number1-2
DOIs
StatePublished - Sep 1 2013

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Keywords

  • AlkB
  • Antibiotic uptake
  • DNA alkylation damage
  • DNA replication and repair
  • Dipyridyl
  • Hydroxyl radicals
  • Mistranslation

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