PMID- 10880451 OWN - NLM STAT- MEDLINE DCOM- 20001005 LR - 20231105 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 19 IP - 13 DP - 2000 Jul 3 TI - Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. PG - 3388-97 AB - 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. FAU - Ulrich, H D AU - Ulrich HD AD - Department of Molecular Cell Biology, Max Planck Institute for Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany. FAU - Jentsch, S AU - Jentsch S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Biopolymers) RN - 0 (Chromatin) RN - 0 (DNA-Binding Proteins) RN - 0 (Fungal Proteins) RN - 0 (MMS2 protein, S cerevisiae) RN - 0 (RAD18 protein, S cerevisiae) RN - 0 (Saccharomyces cerevisiae Proteins) RN - EC 2.3.2.23 (RAD6 protein, S cerevisiae) RN - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 3.6.1.- (Adenosine Triphosphatases) RN - EC 3.6.1.- (RAD5 protein, S cerevisiae) RN - EC 3.6.4.- (DNA Helicases) RN - EC 6.- (Ligases) SB - IM MH - *Adenosine Triphosphatases MH - Biopolymers MH - Cell Nucleus/metabolism MH - Chromatin/metabolism MH - Cytoplasm/metabolism MH - DNA Damage MH - DNA Helicases MH - *DNA Repair MH - DNA-Binding Proteins/*metabolism MH - Fungal Proteins/*metabolism MH - Ligases/*metabolism MH - Protein Binding MH - Saccharomyces cerevisiae/enzymology/metabolism MH - *Saccharomyces cerevisiae Proteins MH - Ubiquitin-Conjugating Enzymes MH - Ubiquitin-Protein Ligases PMC - PMC313941 EDAT- 2000/07/06 11:00 MHDA- 2000/10/07 11:01 PMCR- 2001/07/03 CRDT- 2000/07/06 11:00 PHST- 2000/07/06 11:00 [pubmed] PHST- 2000/10/07 11:01 [medline] PHST- 2000/07/06 11:00 [entrez] PHST- 2001/07/03 00:00 [pmc-release] AID - cdd324 [pii] AID - 10.1093/emboj/19.13.3388 [doi] PST - ppublish SO - EMBO J. 2000 Jul 3;19(13):3388-97. doi: 10.1093/emboj/19.13.3388.