9QPX

BRCA1 BRCT tandem repeat with RNA polymerase II pSer5-CTD peptide

Summary for 9QPX

• Entry DOI: 10.2210/pdb9qpx/pdb
• Descriptor: Breast cancer type 1 susceptibility protein, DNA-directed RNA polymerase II subunit RPB1 (2 entities in total)
• Functional Keywords: brca brct repeat, rna polymerase ii, transcription regulation, dna repair, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 103261.62

Authors

Houser, J.,Klapstova, V.,Sebesta, M. (deposition date: 2025-03-30, release date: 2026-01-14)

Primary citation

Klapstova, V.,Sedova, K.,Houser, J.,Sebesta, M.
Distinct mechanisms of recognition of phosphorylated RNAPII C-terminal domain by BRCT repeats of the BRCA1-BARD1 complex.
J.Biol.Chem., 302:111010-111010, 2025

PubMed Abstract: Transcription competes with other DNA-dependent processes, such as DNA repair, for access to its substrate, DNA. However, the principles governing the interplay between these processes remain poorly understood. Evidence suggests that the BRCA1-BARD1 complex, a key player in the DNA damage response, may act as a mediator of this crosstalk. In this study, we investigated the molecular mechanism underpinning the interaction between RNA polymerase II (RNAPII) and the BRCA1-BARD1 complex, as well as its functional implications. Our findings reveal that the tandem BRCT domain of BRCA1 binds the Ser5-phosphorylated CTD of RNAPII, utilizing a mechanism previously established for other BRCA1 BRCT ligands. Furthermore, we demonstrate that this interaction is critical for the organization of RNAPII into condensates with liquid-like properties. Analysis of disease-associated variants within the BRCT repeats further supports the biological relevance of this condensation. Collectively, our results suggest that the BRCA1-BARD1 complex may coordinate transcription and DNA repair by facilitating the organization of RNAPII into transcription factories.

PubMed: 41354346
DOI: 10.1016/j.jbc.2025.111010

Experimental method

X-RAY DIFFRACTION (3 Å)