Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair

Cell. 1999 Mar 5;96(5):645-53. doi: 10.1016/s0092-8674(00)80575-9.

Abstract

Ubiquitin-conjugating enzyme variant (UEV) proteins resemble ubiquitin-conjugating enzymes (E2s) but lack the defining E2 active-site residue. The MMS2-encoded UEV protein has been genetically implicated in error-free postreplicative DNA repair in Saccharomyces cerevisiae. We show that Mms2p forms a specific heteromeric complex with the UBC13-encoded E2 and is required for the Ubc13p-dependent assembly of polyubiquitin chains linked through lysine 63. A ubc13 yeast strain is UV sensitive, and single, double, and triple mutants of the UBC13, MMS2, and ubiquitin (ubiK63R) genes display a comparable phenotype. These findings support a model in which an Mms2p/Ubc13p complex assembles novel polyubiquitin chains for signaling in DNA repair, and they suggest that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biopolymers / metabolism
  • Cattle
  • DNA Repair / physiology*
  • Fungal Proteins / physiology*
  • Humans
  • Ligases / physiology*
  • Macromolecular Substances
  • Molecular Sequence Data
  • Multigene Family
  • Recombinant Fusion Proteins / physiology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins*
  • Species Specificity
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism*

Substances

  • Biopolymers
  • Fungal Proteins
  • MMS2 protein, S cerevisiae
  • Macromolecular Substances
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligases
  • Ligases