The puzzle of PCNA's many partners

Abstract

The identification of proteins that interact with proliferating cell nuclear antigen (PCNA) has recently been a rapidly expanding field of discovery. PCNA is involved in many aspects of DNA replication and processing, forming a sliding platform that can mediate the interaction of proteins with DNA. It is striking that many proteins bind to PCNA through a small region containing a conserved motif; these include proteins involved in cell cycle regulation as well as those involved in DNA processing. Sequential and regulated binding of motif-containing proteins to PCNA may contribute to the ordering of events during DNA replication and repair. Results from bacteriophages and archaea show that the structural basis for the interaction of this motif with PCNA is extremely ancient. The analysis of how such functional motifs have been recruited to proteins in present day organisms helps us to understand how these complex systems arose from ancestral organisms.

Physical and functional interaction of human nuclear uracil-DNA glycosylase with proliferating cell nuclear antigen

“…A similar observation regarding the p21-PCNA interaction was reported by Flores-Rozas et al [48], who found that on average 2.3 molecules of p21/Cipl (monomer) bound to 1 molecule of PCNA trimer. The N-terminus of UNG2 shares the PCNA consensus binding motif with several proteins involved in DNA replication and repair, including MSH3, MSH6, FEN1, MCMT, and LIG1 [44]. In light of these many interactions, it is attractive to envision a model in which UNG2 participates in a multi-protein complex associated with the replication fork in order to remove uracil residues that result from dUMP incorporation in place of dTMP opposite dAMP.…”

“…The extreme N-terminus of UNG2 bears a consensus PCNA-binding motif shared by p21, MSH6, LIG1, XPG, FEN1, and many other proteins involved in DNA transactions [44]. In a seminal crystal structure of PCNA, a p21 peptide encompassing the binding motif was shown to bind to the interdomain connector loop (IDCL) region of PCNA [25].…”

Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer

“…A PCNA ring may bind to different protein partners at different time and space to carry out specific tasks [3,5,16,17]. We previously found that the level of PCNA is substantially elevated in cancer cells, which is only notable difference between cancer and normal cells with respect to PCNA protein [18].…”

XPG: Its Products and Biological Roles

“…27 The 300 amino acids at the Cterminal end of the protein, beyond the I region, are also engaged in protein-protein interactions; this region contains interaction sites with TFIIH and CSB and a PIP-box motif that mediates an interaction with PCNA. 24,28,29 A second interaction site with TFIIH is consistent with a strong functional interaction between XPG and TFIIH. 30 The functional significance of the interaction of XPG with CSB and PCNA has not yet been established.…”