title: SUMO modification of PCNA is controlled by DNA.
abstract: Post-translational modification by the ubiquitin-like protein SUMO is often regulated by cellular signals that restrict the modification to appropriate situations. Nevertheless, many SUMO-specific ligases do not exhibit much target specificity, and--compared with the diversity of sumoylation substrates--their number is limited. This raises the question of how SUMO conjugation is controlled in vivo. We report here an unexpected mechanism by which sumoylation of the replication clamp protein, PCNA, from budding yeast is effectively coupled to S phase. We find that loading of PCNA onto DNA is a prerequisite for sumoylation in vivo and greatly stimulates modification in vitro. To our surprise, however, DNA binding by the ligase Siz1, responsible for PCNA sumoylation, is not strictly required. Instead, the stimulatory effect of DNA on conjugation is mainly attributable to DNA binding of PCNA itself. These findings imply a change in the properties of PCNA upon loading that enhances its capacity to be sumoylated.
authors.affiliation: Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, UK.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Parker
authors.forename: Andrea
authors.initials: A
authors.lastname: Bucceri
authors.forename: Adelina A
authors.initials: AA
authors.lastname: Davies
authors.forename: Katharina
authors.initials: K
authors.lastname: Heidrich
authors.forename: Hanna
authors.initials: H
authors.lastname: Windecker
authors.forename: Helle D
authors.initials: HD
authors.lastname: Ulrich
mesh_terms: D000483:Alleles; D002843:Chromatin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D008954:Models, Biological; D008957:Models, Genetic; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D025842:SUMO-1 Protein / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry
chemical_list: D002843:Chromatin; D018809:Proliferating Cell Nuclear Antigen; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D004247:DNA; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; C118083:Ulp1 protease; C436837:Siz1 protein, S cerevisiae