Effects of chain length and geometry on the activation of DNA damage bypass by polyubiquitylated PCNA
| Autor: | Tomio S. Takahashi, Jonathan Lowther, Hans-Peter Wollscheid, Helle D. Ulrich |
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| Přispěvatelé: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire des Archées (ARCHEE), Département Microbiologie (Dpt Microbio), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins DNA Repair DNA damage DNA polymerase AcademicSubjects/SCI00010 [SDV]Life Sciences [q-bio] Geometry DNA-Directed DNA Polymerase Saccharomyces cerevisiae Genome Integrity Repair and Replication 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ubiquitin Proliferating Cell Nuclear Antigen Genetics Protein Interaction Maps Polyubiquitin Receptor 030304 developmental biology 0303 health sciences DNA clamp biology Effector Ubiquitination Proliferating cell nuclear antigen DNA-Binding Proteins chemistry biology.protein 030217 neurology & neurosurgery DNA DNA Damage |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2020, ⟨10.1093/nar/gkaa053⟩ Nucleic Acids Research, 2020, ⟨10.1093/nar/gkaa053⟩ |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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