Summary for 7PLO
| Entry DOI | 10.2210/pdb7plo/pdb |
| EMDB information | 13490 13491 13492 13494 |
| Descriptor | DNA replication licensing factor MCM2, DNA replication complex GINS protein PSF1, DNA replication complex GINS protein PSF2, ... (28 entities in total) |
| Functional Keywords | genome stability, dna replication, ubiquitination, termination, replisome, cryo-em, cmg, cul2lrr1, replication, dna, polymerase, helicase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 26 |
| Total formula weight | 1964966.14 |
| Authors | Jones, M.J.,Yeeles, J.T.P.,Deegan, T.D.,Jenkyn-Bedford, M. (deposition date: 2021-09-01, release date: 2021-11-10, Last modification date: 2023-10-18) |
| Primary citation | Jenkyn-Bedford, M.,Jones, M.L.,Baris, Y.,Labib, K.P.M.,Cannone, G.,Yeeles, J.T.P.,Deegan, T.D. A conserved mechanism for regulating replisome disassembly in eukaryotes. Nature, 600:743-747, 2021 Cited by PubMed Abstract: Replisome disassembly is the final step of eukaryotic DNA replication and is triggered by ubiquitylation of the CDC45-MCM-GINS (CMG) replicative helicase. Despite being driven by evolutionarily diverse E3 ubiquitin ligases in different eukaryotes (SCF in budding yeast, CUL2 in metazoa), replisome disassembly is governed by a common regulatory principle, in which ubiquitylation of CMG is suppressed before replication termination, to prevent replication fork collapse. Recent evidence suggests that this suppression is mediated by replication fork DNA. However, it is unknown how SCF and CUL2 discriminate terminated from elongating replisomes, to selectively ubiquitylate CMG only after termination. Here we used cryo-electron microscopy to solve high-resolution structures of budding yeast and human replisome-E3 ligase assemblies. Our structures show that the leucine-rich repeat domains of Dia2 and LRR1 are structurally distinct, but bind to a common site on CMG, including the MCM3 and MCM5 zinc-finger domains. The LRR-MCM interaction is essential for replisome disassembly and, crucially, is occluded by the excluded DNA strand at replication forks, establishing the structural basis for the suppression of CMG ubiquitylation before termination. Our results elucidate a conserved mechanism for the regulation of replisome disassembly in eukaryotes, and reveal a previously unanticipated role for DNA in preserving replisome integrity. PubMed: 34700328DOI: 10.1038/s41586-021-04145-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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