9KEM

Crystal structure of BRD4-BD1 in complex with H2AK5acK9ac

Summary for 9KEM

• Entry DOI: 10.2210/pdb9kem/pdb
• Descriptor: Bromodomain-containing protein 4, H2A(1-15) (3 entities in total)
• Functional Keywords: bromodomain, acetylation, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 56987.94

Authors

Wang, X.D.,Ji, J.H.,Yang, H.W.,Li, Z.B.,Yang, N. (deposition date: 2024-11-05, release date: 2026-06-10, Last modification date: 2026-07-01)

Primary citation

Wang, X.,Ji, J.,Ma, Y.,Liu, L.,Bao, K.,Yang, H.,Li, Z.,Li, T.,Shi, L.,Yang, N.
Structural mechanism of diacetylated histone H2A recognition by Bromodomain-containing protein 4 in Regulation of non-homologous end-joining DNA repair.
Int.J.Biol.Macromol., 368:152638-152638, 2026

PubMed Abstract: Bromodomain-containing protein 4 (BRD4) is well characterized as a histone acetyllysine reader that plays critical roles in the regulation of oncogene transcription. Additionally, BRD4 has been shown to be involved in DNA repair and telomere maintenance in a transcriptionally independent manner. Our previous study revealed that BRD4 inhibits non-homologous end-joining (NHEJ) DNA repair by recognizing the histone H2AK5acK9ac hyperacetylation at DSB sites through its tandem bromodomains (BD1 and BD2), resulting in the accumulation of the BRD4-KU80 protein that impedes the assembly of the DNA repair machinery in mitotic deacetylase complex (MiDAC)-deficient cells. Here we report the structural basis for the recognition of H2AK5acK9ac by BD1 and BD1-BD2 domains, respectively. In particular, we show that Leu92 in BD1 is a key determinant of the H2AK5acK9ac specificity over other diacetyllysine marks on H4, and it negatively regulates NHEJ repair to promote genomic instability in MiDAC-deficient cells. These results reveal a previously unrecognized mode of BRD4-histone interaction and its functional consequences that make a meaningful contribution to chromatin biology and DNA repair.

PubMed: 42173225
DOI: 10.1016/j.ijbiomac.2026.152638

Experimental method

X-RAY DIFFRACTION (1.94 Å)