Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase

Science. 2008 Oct 24;322(5901):597-602. doi: 10.1126/science.1162790.

Abstract

Recent findings suggest important roles for nuclear organization in gene expression. In contrast, little is known about how nuclear organization contributes to genome stability. Epistasis analysis (E-MAP) using DNA repair factors in yeast indicated a functional relationship between a nuclear pore subcomplex and Slx5/Slx8, a small ubiquitin-like modifier (SUMO)-dependent ubiquitin ligase, which we show physically interact. Real-time imaging and chromatin immunoprecipitation confirmed stable recruitment of damaged DNA to nuclear pores. Relocation required the Nup84 complex and Mec1/Tel1 kinases. Spontaneous gene conversion can be enhanced in a Slx8- and Nup84-dependent manner by tethering donor sites at the nuclear periphery. This suggests that strand breaks are shunted to nuclear pores for a repair pathway controlled by a conserved SUMO-dependent E3 ligase.

Publication types

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

MeSH terms

  • Chromatin Immunoprecipitation
  • DNA Breaks, Double-Stranded*
  • DNA Repair
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Gene Conversion
  • Genes, Fungal
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinetics
  • Nuclear Pore / metabolism*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Recombination, Genetic
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Ubiquitin-Protein Ligases / metabolism*
  • Zinc Fingers

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • NUP84 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Saccharomyces cerevisiae Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Slx8 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • SCEI protein, S cerevisiae
  • Deoxyribonucleases, Type II Site-Specific
  • Slx5 protein, S cerevisiae