Work

Distinct mechanisms of recognition of phosphorylated RNAPII C-terminal domain by BRCT repeats of the BRCA1–BARD1 complex

Year: 2025

Type: article

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.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.111010

Authors: V. Klapstova, K. Sedova, J. Houser, M. Sebesta

Institutions: Masaryk University, Central European Institute of Technology – Masaryk University

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,430