論文 - 詳細
| RRC ID | 51356 |
|---|---|
| 著者 | Sonneville R, Moreno SP, Knebel A, Johnson C, Hastie CJ, Gartner A, Gambus A, Labib K. |
| タイトル | CUL-2LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis. |
| ジャーナル | Nat Cell Biol |
| Abstract |
Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2LRR-1 associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2LRR1 as a key regulated step during DNA replication termination. Interestingly, however, CMG persists on chromatin until prophase in worms that lack CUL-2LRR-1, but is then removed by a mitotic pathway that requires the CDC-48 cofactor UBXN-3, orthologous to the human tumour suppressor FAF1. Partial inactivation of lrr-1 and ubxn-3 leads to synthetic lethality, suggesting future approaches by which a deeper understanding of CMG disassembly in metazoa could be exploited therapeutically. |
| 巻・号 | 19(5) |
| ページ | 468-479 |
| 公開日 | 2017-5-1 |
| DOI | 10.1038/ncb3500 |
| PII | ncb3500 |
| PMID | 28368371 |
| PMC | PMC5410169 |
| MeSH | Adenosine Triphosphatases / genetics Adenosine Triphosphatases / metabolism Animals Animals, Genetically Modified Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Chromatin / enzymology* Chromatin / genetics Chromatin Assembly and Disassembly Cullin Proteins / genetics Cullin Proteins / metabolism* DNA / biosynthesis* DNA / genetics Genotype Mitosis* Multiprotein Complexes Oocytes Phenotype RNA Interference S Phase* Time Factors Ubiquitination Valosin Containing Protein Xenopus Proteins / genetics Xenopus Proteins / metabolism Xenopus laevis / genetics Xenopus laevis / metabolism |
| IF | 20.042 |
| 引用数 | 23 |
| リソース情報 | |
| 線虫 | tm3543 |