Dynamics of phosphodiester synthesis by DNA ligase

Proc Natl Acad Sci U S A. 2008 May 13;105(19):6894-9. doi: 10.1073/pnas.0800113105. Epub 2008 May 5.

Abstract

Ligases are essential actors in DNA replication, recombination, and repair by virtue of their ability to seal breaks in the phosphodiester backbone. Ligation proceeds through a nicked DNA-adenylate intermediate (AppDNA), which must be sealed quickly to avoid creating a potentially toxic lesion. Here, we take advantage of ligase-catalyzed AMP-dependent incision of a single supercoiled DNA molecule to observe the step of phosphodiester synthesis in real time. An exponentially distributed number of supercoils was relaxed per successful incision-resealing event, from which we deduce the torque-dependent ligation probability per DNA swivel. Premature dissociation of ligase from nicked DNA-adenylate accounted for approximately 10% of the observed events. The ability of ligase to form a C-shaped protein clamp around DNA is a key determinant of ligation probability per turn and the stability of the ligase-AppDNA intermediate. The estimated rate of phosphodiester synthesis by DNA ligase (400 s(-1)) is similar to the high rates of phosphodiester synthesis by replicative DNA polymerases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / metabolism
  • DNA Ligases / metabolism*
  • DNA Topoisomerases, Type I / metabolism
  • DNA, Superhelical / metabolism
  • DNA-Directed DNA Polymerase / metabolism
  • Models, Molecular
  • Mutant Proteins / metabolism
  • Organophosphates / metabolism*
  • Viral Proteins / metabolism*

Substances

  • DNA, Superhelical
  • Mutant Proteins
  • Organophosphates
  • Viral Proteins
  • Adenosine Monophosphate
  • DNA-Directed DNA Polymerase
  • DNA Topoisomerases, Type I
  • Chlorella virus DNA ligase
  • DNA Ligases