Gene

Cell biology

DNA-binding protein

Biology

DNA replication

Computational biology

DNA clamp

Replication protein A

Genetics

Proliferating cell nuclear antigen

DNA polymerase delta

DNA repair

Polymerase

Transcription factor

Reverse transcriptase

Replication factor C

Polymerase chain reaction

Eukaryotic DNA replication

DNA polymerase

Biomolecules

Proliferating cell nuclear antigen (PCNA) is an essential factor in DNA replication and repair. It forms a homotrimeric ring that embraces the DNA and slides along it, anchoring DNA polymerases and other DNA editing enzymes. It also interacts with regulatory proteins through a sequence motif known as PCNA Interacting Protein box (PIP-box). We here review the latest contributions to knowledge regarding the structure-function relationships in human PCNA, particularly the mechanism of sliding, and of the molecular recognition of canonical and non-canonical PIP motifs. The unique binding mode of the oncogene p15 is described in detail, and the implications of the recently discovered structure of PCNA bound to polymerase δ are discussed. The study of the post-translational modifications of PCNA and its partners may yield therapeutic opportunities in cancer treatment, in addition to illuminating the way PCNA coordinates the dynamic exchange of its many partners in DNA replication and repair.

Human PCNA Structure, Function and Interactions