2ZVM

Crystal structure of PCNA in complex with DNA polymerase iota fragment

Summary for 2ZVM

• Entry DOI: 10.2210/pdb2zvm/pdb
• Related: 2ZVK 2ZVL
• Descriptor: Proliferating cell nuclear antigen, DNA polymerase iota (3 entities in total)
• Functional Keywords: dna replication, pcna, clamp, translesion synthesis, tls, dna polymerase, complex, pip-box, dna polymerase iota, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P12004
• Total number of polymer chains: 6
• Total formula weight: 94028.13

Authors

Hishiki, A.,Hashimoto, H.,Hanafusa, T.,Kamei, K.,Ohashi, E.,Shimizu, T.,Ohmori, H.,Sato, M. (deposition date: 2008-11-11, release date: 2009-02-10, Last modification date: 2023-11-01)

Primary citation

Hishiki, A.,Hashimoto, H.,Hanafusa, T.,Kamei, K.,Ohashi, E.,Shimizu, T.,Ohmori, H.,Sato, M.
Structural Basis for Novel Interactions between Human Translesion Synthesis Polymerases and Proliferating Cell Nuclear Antigen
J.Biol.Chem., 284:10552-10560, 2009

PubMed Abstract: Translesion synthesis (TLS) is a DNA damage tolerance mechanism that allows continued DNA synthesis, even in the presence of damaged DNA templates. Mammals have multiple DNA polymerases specialized for TLS, including Poleta, Poliota, and Polkappa. These enzymes show preferential bypass for different lesions. Proliferating cell nuclear antigen (PCNA), which functions as a sliding clamp for the replicative polymerase Poldelta, also interacts with the three TLS polymerases. Although many PCNA-binding proteins have a highly conserved sequence termed the PCNA-interacting protein box (PIP-box), Poleta, Poliota, and Polkappa have a noncanonical PIP-box sequence. In response to DNA damage, Lys-164 of PCNA undergoes ubiquitination by the RAD6-RAD18 complex, and the ubiquitination is considered to facilitate TLS. Consistent with this, these three TLS polymerases have one or two ubiquitin binding domains and are recruited to replication forks via interactions with ubiquitinated PCNA involving the noncanonical PIP-box and ubiquitin binding domain. However, it is unclear how these TLS polymerases interact with PCNA. To address the structural basis for interactions between different TLS polymerases and PCNA, we determined crystal structures of PCNA bound to peptides containing the noncanonical PIP-box of these polymerases. We show that the three PIP-box peptides interact with PCNA in different ways, both from one another and from canonical PIP-box peptides. Especially, the PIP-box of Poliota adopts a novel structure. Furthermore, these structures enable us to speculate how these TLS polymerases interact with Lys-164-monoubiquitinated PCNA. Our results will provide clues to understanding the mechanism of preferential recruitment of TLS polymerases to the stalled forks.

PubMed: 19208623
DOI: 10.1074/jbc.M809745200

Experimental method

X-RAY DIFFRACTION (2.3 Å)