4S0N

Crystal Structure of HLTF HIRAN Domain bound to DNA

4S0N の概要

• エントリーDOI: 10.2210/pdb4s0n/pdb
• 分子名称: Helicase-like transcription factor, 5'-D(*TP*TP*TP*TP*TP*TP*TP*TP*TP*T)-3', THYMIDINE-5'-PHOSPHATE, ... (6 entities in total)
• 機能のキーワード: alpha+beta, dna 3'-end binding, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : Q14527
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 69641.26

構造登録者

Chavez, D.A.,Eichman, B.F. (登録日: 2015-01-02, 公開日: 2015-05-27, 最終更新日: 2025-02-12)

主引用文献

Kile, A.C.,Chavez, D.A.,Bacal, J.,Eldirany, S.,Korzhnev, D.M.,Bezsonova, I.,Eichman, B.F.,Cimprich, K.A.
HLTF's Ancient HIRAN Domain Binds 3' DNA Ends to Drive Replication Fork Reversal.
Mol.Cell, 58:1090-1100, 2015

PubMed Abstract: Stalled replication forks are a critical problem for the cell because they can lead to complex genome rearrangements that underlie cell death and disease. Processes such as DNA damage tolerance and replication fork reversal protect stalled forks from these events. A central mediator of these DNA damage responses in humans is the Rad5-related DNA translocase, HLTF. Here, we present biochemical and structural evidence that the HIRAN domain, an ancient and conserved domain found in HLTF and other DNA processing proteins, is a modified oligonucleotide/oligosaccharide (OB) fold that binds to 3' ssDNA ends. We demonstrate that the HIRAN domain promotes HLTF-dependent fork reversal in vitro through its interaction with 3' ssDNA ends found at forks. Finally, we show that HLTF restrains replication fork progression in cells in a HIRAN-dependent manner. These findings establish a mechanism of HLTF-mediated fork reversal and provide insight into the requirement for distinct fork remodeling activities in the cell.

PubMed: 26051180
DOI: 10.1016/j.molcel.2015.05.013

実験手法

X-RAY DIFFRACTION (1.501 Å)