Repair of helix-stabilizing anthramycin-N2 guanine DNA adducts by UVRA and UVRB proteins

Moon shong Tang, Michael E. Nazimiec, Richard P. Doisy, James R. Pierce, Laurence H. Hurley, Benjamin E. Alderete

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The transfectivity of anthramycin (Atm)-modified φX174 replicative form (RF) DNA in Escherichia coli is lower in uvrA and uvrB mutant cells but much higher in uvrC mutant cells compared to wild-type cells. Pretreatment of the Atm-modified phage DNA with purified UVRA and UVRB significantly increases the transfectivity of the DNA in uvrA or uvrB mutant cells. This pretreatment greatly reduces the UVRABC nuclease-sensitive sites (UNSS) and Atm-induced absorbance at 343 nm in the Atm-modified DNA without producing apurinic sites. The reduction of UNSS is proportional to the concentrations of UVRA and UVRB and the enzyme-DNA incubation time and requires ATP. We conclude that there are two different mechanisms for repairing Atm-N2 guanine adducts by UVR proteins: (1) UVRA and UVRB bind to the Atm-N2 guanine double-stranded DNA region and consequently release the Atm from the adducted guanine; (2) UVRABC makes an incision at both sides of the Atm-DNA adduct. The latter mechanism produces potentially lethal double-strand DNA breaks in Atm-modified φX174 RF DNA in vitro.

Original languageEnglish (US)
Pages (from-to)855-866
Number of pages12
JournalJournal of Molecular Biology
Volume220
Issue number4
DOIs
StatePublished - Aug 20 1991
Externally publishedYes

Keywords

  • DNA-damage
  • UVR
  • anthramycin
  • repair

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Repair of helix-stabilizing anthramycin-N2 guanine DNA adducts by UVRA and UVRB proteins'. Together they form a unique fingerprint.

Cite this