9VGW

Crystal structure of human PCNA in complex with REV1 PIP-box

Summary for 9VGW

• Entry DOI: 10.2210/pdb9vgw/pdb
• Descriptor: Proliferating cell nuclear antigen, peptide from DNA repair protein REV1 (3 entities in total)
• Functional Keywords: nuclear protein, dna replication, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 90931.49

Authors

Hashimoto, H.,Hishiki, A. (deposition date: 2025-06-15, release date: 2025-09-10, Last modification date: 2025-11-19)

Primary citation

Hishiki, A.,Hoshino, N.,Okawara, K.,Fuchigami, S.,Hara, K.,Hashimoto, H.
Identification of a PCNA-binding motif in human translesion DNA polymerase REV1 and structural basis of its interaction with PCNA.
J.Biochem., 178:315-324, 2025

PubMed Abstract: REV1 is a eukaryotic error-prone DNA polymerase belonging to the Y-family, with a central role in translesion DNA synthesis (TLS) to continue DNA replication even in the presence of DNA damage in the template strand. TLS is stimulated by monoubiquitination of proliferating cell nuclear antigen (PCNA), a toroidal-shaped protein functioning as a scaffold for DNA polymerases and repair enzymes. Mammals possess four types of Y-family DNA polymerases: Pol η, Pol κ, Pol ι and REV1. Among those, Pol η, Pol κ and Pol ι interact with PCNA through PCNA-binding motifs, low-affinity variants of PCNA-interacting protein box (PIP-box). To date, several studies have reported that REV1 interacts with PCNA, but identified PCNA-binding regions are inconsistent; therefore, a structural basis for interaction between REV1 and PCNA also remains unclear. Here, we identified a signature sequence conserved within vertebrates REV1 responsible for PCNA-binding. Furthermore, we unveiled a mechanism underlying the physical interaction between the PCNA-binding motif of human REV1 and PCNA by X-ray crystallography, thus revealing that REV1 binds to PCNA through a PIP-box variant located in the C-terminal side of the little finger domain. Our study provides a convincing answer for a long-standing controversy regarding the physical interaction between REV1 and PCNA.

PubMed: 40888629
DOI: 10.1093/jb/mvaf054

Experimental method

X-RAY DIFFRACTION (2.7 Å)