PCNA Structure and Function: Insights from Structures of PCNA Complexes and Post-translationally Modified PCNA

Abstract

Proliferating cell nuclear antigen (PCNA), the eukaryotic DNA sliding clamp, forms a ring-shaped homo-trimer that encircles double-stranded DNA. This protein is best known for its ability to confer high processivity to replicative DNA polymerases. However, it does far more than this, because it forms a mobile platform on the DNA that recruits many of the proteins involved in DNA replication, repair, and recombination to replication forks. X-ray crystal structures of PCNA bound to PCNA-binding proteins have provided insights into how PCNA recognizes its binding partners and recruits them to replication forks. More recently, X-ray crystal structures of ubiquitin-modified and SUMO-modified PCNA have provided insights into how these post-translational modifications alter the specificity of PCNA for some of its binding partners. This article focuses on the insights gained from structural studies of PCNA complexes and post-translationally modified PCNA.

A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp

“…The canonical PIP motif is a weak consensus sequence of eight amino acids QXXhXXaa where ‘h’ is a moderately hydrophobic amino acid and ‘a’ is an aromatic residue (9). The PIP-containing proteins bind to the PCNA trimer in a small hydrophobic cavity near the IDCL [reviewed in: (10)].…”

The cell death and DNA damages caused by the Tet-On regulating HSV-tk/GCV suicide gene system in MCF-7 cells

“…Genotoxicity or nongenotoxicity stress signals, such as DNA damage, expression of abnormal growth signals, chemical therapeutic drugs treatment, ultraviolet ray can promote protein kinases to react with some kinds of amino acids located at p53 Nterminal (Ser6, Ser9, Ser15, Ser20, Ser28) or C-terminal and make those amino acids phosphorylated by protein kinases, such as ATM, CK1 and Chk2. Ultimately, the cell growth inhibition, apoptosis, adaption for DNA damage and survival [14] will occur in breast cancer cells.…”

Characterization of human translesion DNA synthesis across a UV-induced DNA lesion

“…A recent study from our lab demonstrated that assembly/disassembly of a pol δ holoenzyme and continuous DNA synthesis by a pol δ holoenzyme are both independent of PCNA monoubiquitination (Hedglin et al, 2016). The ubiquitin moieties attached to PCNA do not alter the conformation of the sliding clamp ring (Dieckman et al, 2012) nor do they shelter the region of PCNA that interacts with DNA pols (Tsutakawa et al, 2011, 2015). Hence, monoubiquitination of PCNA is not envisioned to have any effect on DNA synthesis by a pol ε holoenzyme on a leading strand template.…”