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Acetylation of PCNA Sliding Surface by Eco1 Promotes Genome Stability through Homologous Recombination
- Source :
- Molecular Cell. 65:78-90
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- During DNA replication, proliferating cell nuclear antigen (PCNA) adopts a ring-shaped structure to promote processive DNA synthesis, acting as a sliding clamp for polymerases. Known posttranslational modifications function at the outer surface of the PCNA ring to favor DNA damage bypass. Here, we demonstrate that acetylation of lysine residues at the inner surface of PCNA is induced by DNA lesions. We show that cohesin acetyltransferase Eco1 targets lysine 20 at the sliding surface of the PCNA ring in vitro and in vivo in response to DNA damage. Mimicking constitutive acetylation stimulates homologous recombination and robustly suppresses the DNA damage sensitivity of mutations in damage tolerance pathways. In comparison to the unmodified trimer, structural differences are observed at the interface between protomers in the crystal structure of the PCNA-K20ac ring. Thus, acetylation regulates PCNA sliding on DNA in the presence of DNA damage, favoring homologous recombination linked to sister-chromatid cohesion.
- Subjects :
- Models, Molecular
0301 basic medicine
Saccharomyces cerevisiae Proteins
Genotype
Protein Conformation
DNA repair
DNA damage
Saccharomyces cerevisiae
Chromatids
Genomic Instability
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
Acetyltransferases
Proliferating Cell Nuclear Antigen
Humans
Molecular Biology
DNA Polymerase III
DNA clamp
030102 biochemistry & molecular biology
biology
Lysine
DNA replication
Nuclear Proteins
Recombinational DNA Repair
Acetylation
Cell Biology
Molecular biology
Proliferating cell nuclear antigen
Cell biology
Phenotype
030104 developmental biology
chemistry
Mutation
biology.protein
DNA mismatch repair
Chromosomes, Fungal
Homologous recombination
Protein Processing, Post-Translational
DNA
DNA Damage
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....5b11608969187600af2839d2e6398d1d