2ZVL

Crystal structure of PCNA in complex with DNA polymerase kappa fragment

2ZVL の概要

• エントリーDOI: 10.2210/pdb2zvl/pdb
• 関連するPDBエントリー: 2ZVK 2ZVM
• 分子名称: Proliferating cell nuclear antigen, DNA polymerase kappa, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: dna replication, pcna, clamp, translesion synthesis, tls, dna polymerase, tls polymerase, complex, pip-box, dna polymerase kappa, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: P12004
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 183739.30

構造登録者

Hishiki, A.,Hashimoto, H.,Hanafusa, T.,Kamei, K.,Ohashi, E.,Shimizu, T.,Ohmori, H.,Sato, M. (登録日: 2008-11-11, 公開日: 2009-02-10, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)