Rtt107 Is a Multi-functional Scaffold Supporting Replication Progression with Partner SUMO and Ubiquitin Ligases

Mol Cell. 2015 Oct 15;60(2):268-79. doi: 10.1016/j.molcel.2015.08.023. Epub 2015 Oct 1.

Abstract

Elucidating the individual and collaborative functions of genome maintenance factors is critical for understanding how genome duplication is achieved. Here, we investigate a conserved scaffold in budding yeast, Rtt107, and its three partners: a SUMO E3 complex, a ubiquitin E3 complex, and Slx4. Biochemical and genetic findings show that Rtt107 interacts separately with these partners and contributes to their individual functions, including a role in replisome sumoylation. We also provide evidence that Rtt107 associates with replisome components, and both itself and its associated E3s are important for replicating regions far from initiation sites. Corroborating these results, replication defects due to Rtt107 loss and genotoxic sensitivities in mutants of Rtt107 and its associated E3s are rescued by increasing replication initiation events through mutating two master repressors of late origins, Mrc1 and Mec1. These findings suggest that Rtt107 functions as a multi-functional platform to support replication progression with its partner E3 enzymes.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Replication*
  • Endodeoxyribonucleases / genetics*
  • Endodeoxyribonucleases / metabolism
  • Gene Expression Regulation, Fungal*
  • Genome, Fungal
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mutation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • SUMO-1 Protein / genetics*
  • SUMO-1 Protein / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sumoylation
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • MRC1 protein, S cerevisiae
  • Nuclear Proteins
  • RTT107 protein, S cerevisiae
  • SUMO-1 Protein
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligases
  • MEC1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Endodeoxyribonucleases
  • SLX4 protein, S cerevisiae