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BRCA1 exon 11 binds to TOPBP1 to mediate resection

ABSTRACT: Approximately 60% of the tumour suppressor protein BRCA1 is encoded by a single exon. Many tumours carry mutations in this exon, often resulting in exon skipping and thus a protein of a severely reduced size. Although none of the well-described protein domains of BRCA1 are encoded by this exon 11, the protein lacking this part shows an hypomorphic activity in homologous recombination. To better understand the function of this large exon, we performed proteomic analyses to identify interaction partners via this part of the protein. Here, we report a DNA damage- and phospho-dependent interaction of TOPBP1 to BRCA1 exon 11. Mechanistically, this interaction is required for BRCA1 exon 11’s role in resection during homologous recombination. In contrast, the interaction is not required for TOPBP1’s role in ATR activation. Our data are an important contribution to better understand this relatively poorly characterized part of the BRCA1 protein.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Román González-Prieto

LAB HEAD: Román González Prieto

PROVIDER: PXD079087 | Pride | 2026-07-29

REPOSITORIES: Pride

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