5UIY

Structure of Bromodomain from human BAZ1A

5UIY の概要

• エントリーDOI: 10.2210/pdb5uiy/pdb
• 分子名称: Bromodomain adjacent to zinc finger domain protein 1A, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• 機能のキーワード: baz1a, bromodomain, dna-damage, acf, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: Q9NRL2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 53633.24

構造登録者

Oppikofer, M.,Sudhamsu, J. (登録日: 2017-01-16, 公開日: 2017-07-12, 最終更新日: 2024-03-06)

主引用文献

Oppikofer, M.,Sagolla, M.,Haley, B.,Zhang, H.M.,Kummerfeld, S.K.,Sudhamsu, J.,Flynn, E.M.,Bai, T.,Zhang, J.,Ciferri, C.,Cochran, A.G.
Non-canonical reader modules of BAZ1A promote recovery from DNA damage.
Nat Commun, 8:862-862, 2017

PubMed Abstract: Members of the ISWI family of chromatin remodelers mobilize nucleosomes to control DNA accessibility and, in some cases, are required for recovery from DNA damage. However, it remains poorly understood how the non-catalytic ISWI subunits BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical gatekeeper residue and binds relatively weakly to acetylated histone peptides. Using CRISPR-Cas9-mediated genome editing we find that BAZ1A and BAZ1B each recruit SMARCA5 to sites of damaged chromatin and promote survival. Genetic engineering of structure-designed bromodomain and plant homeodomain mutants reveals that reader modules of BAZ1A and BAZ1B, even when non-standard, are critical for DNA damage recovery in part by regulating ISWI factors loading at DNA lesions and supporting transcriptional programs required for survival.ISWI chromatin remodelers regulate DNA accessibility and have been implicated in DNA damage repair. Here, the authors uncover functions, in response to DNA damage, for the bromodomain of the ISWI subunit BAZ1B and for the non-canonical PHD and bromodomain modules of the paralog BAZ1A.

PubMed: 29021563
DOI: 10.1038/s41467-017-00866-0

実験手法

X-RAY DIFFRACTION (1.687 Å)