New therapeutic approaches that can accelerate neutrophil apoptosis under inflammatory conditions to enhance the resolution of inflammation are now under study. Neutrophils are deprived of proliferative capacity and have a tightly controlled lifespan to avoid their persistence at the site of injury. We have recently described that the proliferating cell nuclear antigen (PCNA), a nuclear factor ...

The proliferating cell nuclear antigen (PCNA) is a processivity subunit for eukaryotic DNA polymerase delta. We present biochemical evidence that yeast PCNA likely adopts a toroidal structure containing an inside cavity through which double-stranded DNA slides. A comparative study of DNA replication reactions on circular versus linear model substrates shows that PCNA can only interact productiv...

Correspondence to Stuart A. Aaronson: [email protected] Abbreviations used in this paper: CM, conditioned medium; dnTCF4, dominantnegative TCF4; ERK, extracellular receptor-dependent kinase; HA, hydroxyapatite; hMSC, human MSC; MSC, mesenchymal stem cell; Osx, osterix; PCNA, proliferating cell nuclear antigen; shRNA, short hairpin RNA; TCF, T cell factor; TCP, tri-Ca phosphate. Introduction

During DNA replication and repair, many proteins bind to and dissociate in a highly specific and ordered manner from proliferating cell nuclear antigen (PCNA). We describe a combined approach of in silico searches at the genome level and combinatorial peptide synthesis to investigate the binding properties of hundreds of short PCNA-interacting peptides (PIP-peptides) to archaeal and eukaryal PC...

The cell cycle regulator p21 interacts with and inhibits the DNA replication and repair factor proliferating cell nuclear antigen (PCNA). We have defined a 39 amino acid fragment of p21 which is sufficient to bind PCNA with high affinity (Kd 10-20 nM). This peptide can inhibit DNA replication in vitro and microinjection of a GST fusion protein containing this domain inhibited S phase in vivo. D...

The intranuclear distribution of newly replicated DNA and of the proliferating cell nuclear antigen (PCNA) was mapped by confocal laser scanning microscopy after simultaneous immunofluorescent labelling of incorporated bromodeoxyuridine (BrdUrd) and PCNA. A mild hydrolysis with HCl followed by an enzymic digestion of DNA was used to produce single-stranded DNA required for BrdUrd immunorevelati...

In this issue, a study by Groehler and Lannigan (2010. J. Cell Biol. doi:10.1083/jcb.201002124) sheds light on the regulation of proliferating cell nuclear antigen (PCNA) turnover and how it is counteracted by the small chromatin-bound kinase ERK8 (extracellular signal-regulated kinase 8). Importantly, inactivation of ERK8 results in genome instability and is associated with cell transformation.