Function
Proliferating Cell Nuclear Antigen (PCNA) is a protein that acts as a DNA sliding clamp. It forms a homotrimer encircling the DNA and binds other peptides means known as PCNA interacting proteins (PIPs). It acts as a processivity factor for DNA polymerases and other enzymes which act upon DNA. Examples of such are DNA polymerase (Dpo) δ in eukaryotic cells[1]. The increases in processivity are very pronounced. The number of basepairs processed before complex dissociation occurs is increased more than a thousandfold (~10bp[2] to ~80kbp[3]) and the speed of nucleotide incorporation rises about a hundredfold [4].
Relevance
PCNA is featured in many cellular pathways involving DNA. [FEN1] bound to PCNA acts as a flap endonuclease and cleaves a displaced ssDNA (flap) containing oxidatively damaged dideoxyribose residue [5]. As stated above PCNA is also vital to formation of the procesive complex for DNA replication [6] and is featured even in gene expression and transcription when bound to [GADD45A] [7]. Thus PCNA is relevant in research and even medicine.
PCNA is useful in the diagnosis of high-grade dysplasia[8].
Structural highlights
p15 regulates DNA replication and repair by binding to PCNA. PCNA-p15 peptide complex shows the and has [9]. Of interest is the binding site contained at each face of the PCNA ring. Said site is formed by a C-terminal domain formed groove and an interdomain connecting loop (IDCL). Some partners do bind to the N-terminal domain as well. There are multiple PIP binding motifs, but the most common one is QxxΨxx∇∇ (where Ψ is a hydrophobic residue and ∇ is either the aromatic residue F or Y) [10][11]
Known mutations
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S228I
Diseases
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3D Structures of Proliferating Cell Nuclear Antigen
Proliferating cell nuclear antigen 3D structures
