Article
- The EMBO Journal (2008) 27, 2422 - 2431
- doi:10.1038/emboj.2008.162
Published online: 14 August 2008
Subject Categories:
SUMO modification of PCNA is controlled by DNAEMBO Open
Joanne L Parker1, Andrea Bucceri1,a, Adelina A Davies1, Katharina Heidrich1,b, Hanna Windecker1,c and Helle D Ulrich1
- Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, UK
Correspondence to:
Helle D Ulrich, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK. Tel.: +44 1707 625821; Fax: +44 1707 625750; E-mail: helle.ulrich@cancer.org.uk
aPresent address: BioMed Central, Middlesex House, 34-42 Cleveland Street, London W1T 4LB, UK
bPresent address: Max Planck Institute for Plant Breeding Research, Department of Molecular Phytopathology, Carl-von-Linné-Weg 10, 50829 Cologne, Germany
cPresent address: Friedrich Miescher Laboratory of the Max Planck Society, Spemannstrasse 39, 72076 Tübingen, Germany
Received 2 April 2008; Accepted 25 July 2008
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.
Keywords:
- clamp loader,
- DNA replication,
- PCNA,
- SUMO,
- SUMO ligase
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