4XHU

The complex structure of Timeless_PAB and PARP-1_catalytic domain

4XHU の概要

• エントリーDOI: 10.2210/pdb4xhu/pdb
• 関連するPDBエントリー: 4XHT 4XHW
• 分子名称: Poly [ADP-ribose] polymerase 1, Protein timeless homolog, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: dna damage response, transferase-replication complex, transferase/replication
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: P09874 Q9UNS1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 103896.36

構造登録者

Xie, S.,Qian, C. (登録日: 2015-01-06, 公開日: 2015-09-30, 最終更新日: 2024-10-09)

主引用文献

Xie, S.,Mortusewicz, O.,Ma, H.T.,Herr, P.,Poon, R.R.,Helleday, T.,Qian, C.
Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair.
Mol.Cell, 60:163-176, 2015

PubMed Abstract: Human Timeless helps stabilize replication forks during normal DNA replication and plays a critical role in activation of the S phase checkpoint and proper establishment of sister chromatid cohesion. However, it remains elusive whether Timeless is involved in the repair of damaged DNA. Here, we identify that Timeless physically interacts with PARP-1 independent of poly(ADP-ribosyl)ation. We present high-resolution crystal structures of Timeless PAB (PARP-1-binding domain) in free form and in complex with PARP-1 catalytic domain. Interestingly, Timeless PAB domain specifically recognizes PARP-1, but not PARP-2 or PARP-3. Timeless-PARP-1 interaction does not interfere with PARP-1 enzymatic activity. We demonstrate that rapid and transient accumulation of Timeless at laser-induced DNA damage sites requires PARP-1, but not poly(ADP-ribosyl)ation and that Timeless is co-trapped with PARP-1 at DNA lesions upon PARP inhibition. Furthermore, we show that Timeless and PARP-1 interaction is required for efficient homologous recombination repair.

PubMed: 26344098
DOI: 10.1016/j.molcel.2015.07.031

実験手法

X-RAY DIFFRACTION (2.089 Å)