Intrinsic flexibility of ubiquitin on proliferating cell nuclear antigen (PCNA) in translesion synthesis

J Biol Chem. 2012 Nov 9;287(46):39216-23. doi: 10.1074/jbc.M112.389890. Epub 2012 Sep 18.

Abstract

Ubiquitin conjugation provides a crucial signaling role in hundreds of cellular pathways; however, a structural understanding of ubiquitinated substrates is lacking. One important substrate is monoubiquitinated PCNA (PCNA-Ub), which signals for recruitment of damage-tolerant polymerases in the translesion synthesis (TLS) pathway of DNA damage avoidance. We use a novel and efficient enzymatic method to produce PCNA-Ub at high yield with a native isopeptide bond and study its Usp1/UAF1-dependent deconjugation. In solution we find that the ubiquitin moiety is flexible relative to the PCNA, with its hydrophobic patch mostly accessible for recruitment of TLS polymerases, which promotes the interaction with polymerase η. The studies are a prototype for the nature of the ubiquitin modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysics / methods
  • Chromatography, Gel
  • DNA Damage
  • DNA Repair
  • DNA Replication
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism
  • Humans
  • Light
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Proliferating Cell Nuclear Antigen / chemistry*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Scattering, Radiation
  • Scattering, Small Angle
  • Signal Transduction
  • Ubiquitin / chemistry*

Substances

  • Proliferating Cell Nuclear Antigen
  • Ubiquitin
  • DNA-Directed DNA Polymerase
  • Rad30 protein