Effects of chain length and geometry on the activation of DNA damage bypass by polyubiquitylated PCNA.
DNA Damage
/ genetics
DNA Repair
/ genetics
DNA Replication
/ genetics
DNA-Binding Proteins
/ genetics
DNA-Directed DNA Polymerase
/ genetics
Polyubiquitin
/ genetics
Proliferating Cell Nuclear Antigen
/ genetics
Protein Interaction Maps
/ genetics
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Ubiquitin
/ genetics
Ubiquitination
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
06 04 2020
06 04 2020
Historique:
accepted:
30
01
2020
revised:
15
01
2020
received:
28
05
2019
pubmed:
6
2
2020
medline:
23
5
2020
entrez:
4
2
2020
Statut:
ppublish
Résumé
Ubiquitylation of the eukaryotic sliding clamp, PCNA, activates a pathway of DNA damage bypass that facilitates the replication of damaged DNA. In its monoubiquitylated form, PCNA recruits a set of damage-tolerant DNA polymerases for translesion synthesis. Alternatively, modification by K63-linked polyubiquitylation triggers a recombinogenic process involving template switching. Despite the identification of proteins interacting preferentially with polyubiquitylated PCNA, the molecular function of the chain and the relevance of its K63-linkage are poorly understood. Using genetically engineered mimics of polyubiquitylated PCNA, we have now examined the properties of the ubiquitin chain required for damage bypass in budding yeast. By varying key parameters such as the geometry of the junction, cleavability and capacity for branching, we demonstrate that either the structure of the ubiquitin-ubiquitin junction or its dynamic assembly or disassembly at the site of action exert a critical impact on damage bypass, even though known effectors of polyubiquitylated PCNA are not strictly linkage-selective. Moreover, we found that a single K63-junction supports substantial template switching activity, irrespective of its attachment site on PCNA. Our findings provide insight into the interrelationship between the two branches of damage bypass and suggest the existence of a yet unidentified, highly linkage-selective receptor of polyubiquitylated PCNA.
Identifiants
pubmed: 32009145
pii: 5721208
doi: 10.1093/nar/gkaa053
pmc: PMC7102961
doi:
Substances chimiques
DNA-Binding Proteins
0
Proliferating Cell Nuclear Antigen
0
RAD18 protein, S cerevisiae
0
Saccharomyces cerevisiae Proteins
0
Ubiquitin
0
Polyubiquitin
120904-94-1
DNA-Directed DNA Polymerase
EC 2.7.7.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3042-3052Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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