Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair.
Two ubiquitin-conjugating enzymes, RAD6 and the heteromeric UBC13-MMS2 complex, have been implicated in post-replicative DNA damage repair in yeast. Here we provide a mechanistic basis for cooperation between the two enzymes. We show that two chromatin-associated RING finger proteins, RAD18 and RAD5, play a central role in mediating physical contacts ... between the members of the RAD6 pathway. RAD5 recruits the UBC13-MMS2 complex to DNA by means of its RING finger domain. Moreover, RAD5 association with RAD18 brings UBC13-MMS2 into contact with the RAD6-RAD18 complex. Interaction between the two RING finger proteins thus promotes the formation of a heteromeric complex in which the two distinct ubiquitin-conjugating activities of RAD6 and UBC13-MMS2 can be closely coordinated. Surprisingly, UBC13 and MMS2 are largely cytosolic proteins, but DNA damage triggers their redistribution to the nucleus. These findings suggest a mechanism by which the activity of this DNA repair pathway could be regulated.
Mesh Terms:
Adenosine Triphosphatases, Biopolymers, Cell Nucleus, Chromatin, Cytoplasm, DNA Damage, DNA Helicases, DNA Repair, DNA-Binding Proteins, Fungal Proteins, Ligases, Protein Binding, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Adenosine Triphosphatases, Biopolymers, Cell Nucleus, Chromatin, Cytoplasm, DNA Damage, DNA Helicases, DNA Repair, DNA-Binding Proteins, Fungal Proteins, Ligases, Protein Binding, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
EMBO J.
Date: Jul. 03, 2000
PubMed ID: 10880451
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