title: Proliferating cell nuclear antigen structure and interactions: too many partners for one dancer?
abstract: PCNA is the DNA sliding clamp found in eukaryotes and archaebacteria. Sliding clamps were first described as processivity factors in DNA replication. They consist of multimeric, toroidal-shaped structures with pseudo-sixfold symmetry that encircle the DNA duplex and tether the replicative polymerases to the genomic template. Later, it was found that PCNA serves as a docking platform where other proteins dock to carry out different DNA metabolic processes. The structure of the bacterial clamp bound to a short primed DNA shows a tilted duplex in the central channel, which is lined by α-helices with net positive charges. Many of the proteins reported to interact with PCNA do so via the PCNA Interaction Protein sequence (PIP-box). The structures of several proteins and peptides bound to PCNA show a common binding mode, but it is still unknown how the many different partners compete for binding and exert their enzymatic and regulatory functions. Furthermore, the literature contains many reports on proteins that directly bind to PCNA as detected by different methods, but only few of the putative complexes have been examined in detail by quantitative analytical techniques or high-resolution structural methods. Some of the reported interactions are not observed in solution using the pure proteins, indicating that the direct interaction is nonexistent or very weak and is likely mediated by other factors. We review here the current knowledge on PCNA interactions from a structural point of view, with a focus on human proteins and highlighting the questions that remain to be answered.
authors.affiliation: Structural Biology Unit, CIC bioGUNE, Derio, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: De Biasio
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D004247:DNA