Intrinsic stability and oligomerization dynamics of DNA processivity clamps

Nucleic Acids Res. 2014 Jun;42(10):6476-86. doi: 10.1093/nar/gku255. Epub 2014 Apr 11.

Abstract

Sliding clamps are ring-shaped oligomeric proteins that are essential for processive deoxyribonucleic acid replication. Although crystallographic structures of several clamps have been determined, much less is known about clamp structure and dynamics in solution. Here, we characterized the intrinsic solution stability and oligomerization dynamics of the homodimeric Escherichia coli β and the homotrimeric Saccharomyces cerevisiae proliferating cell nuclear antigen (PCNA) clamps using single-molecule approaches. We show that E. coli β is stable in solution as a closed ring at concentrations three orders of magnitude lower than PCNA. The trimeric structure of PCNA results in slow subunit association rates and is largely responsible for the lower solution stability. Despite this large difference, the intrinsic lifetimes of the rings differ by only one order of magnitude. Our results show that the longer lifetime of the E. coli β dimer is due to more prominent electrostatic interactions that stabilize the subunit interfaces.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA Polymerase III / chemistry
  • DNA Polymerase III / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / chemistry
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Multimerization
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Spectrometry, Fluorescence

Substances

  • Escherichia coli Proteins
  • Proliferating Cell Nuclear Antigen
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • beta subunit, DNA polymerase III
  • DNA Polymerase III