CMG helicase disassembly is controlled by replication fork DNA, replisome components and a ubiquitin threshold.
CMG helicase
DNA replication
S. cerevisiae
chromosomes
gene expression
termination
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
17 08 2020
17 08 2020
Historique:
received:
24
06
2020
accepted:
14
08
2020
pubmed:
18
8
2020
medline:
26
2
2021
entrez:
18
8
2020
Statut:
epublish
Résumé
The eukaryotic replisome assembles around the CMG helicase, which stably associates with DNA replication forks throughout elongation. When replication terminates, CMG is ubiquitylated on its Mcm7 subunit and disassembled by the Cdc48/p97 ATPase. Until now, the regulation that restricts CMG ubiquitylation to termination was unknown, as was the mechanism of disassembly. By reconstituting these processes with purified budding yeast proteins, we show that ubiquitylation is tightly repressed throughout elongation by the Y-shaped DNA structure of replication forks. Termination removes the repressive DNA structure, whereupon long K48-linked ubiquitin chains are conjugated to CMG-Mcm7, dependent on multiple replisome components that bind to the ubiquitin ligase SCF
Identifiants
pubmed: 32804080
doi: 10.7554/eLife.60371
pii: 60371
pmc: PMC7462611
doi:
pii:
Substances chimiques
Recombinant Proteins
0
Ubiquitin
0
DNA
9007-49-2
DNA Helicases
EC 3.6.4.-
Valosin Containing Protein
EC 3.6.4.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : 24558
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12016/13
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C578/A24558
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C578/A25669
Pays : United Kingdom
Informations de copyright
© 2020, Deegan et al.
Déclaration de conflit d'intérêts
TD, PM, RF, CP, KL No competing interests declared
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