ArticleCancer science2022
BRCA1 transports the DNA damage signal for CDDP-induced centrosome amplification through the centrosomal Aurora A.
Article in Cancer science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Disrupted STIL-BRCA1 axis causes centrosome amplification and genomic instability.FEBS letters · 2026Article
- Indium (III) chloride inhibits testicular Leydig cell proliferation by disrupting centrosome copy numbers.Molecular medicine reports · 2026Article
- Evaluating homologous recombination activity in tissues to predict the risk of hereditary breast and ovarian cancer and olaparib sensitivity.Scientific reports · 2024Article
- BRCA1 transports the DNA damage signal for CDDP-induced centrosome amplification through the centrosomal Aurora A.Cancer science · 2022Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage-induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S-G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo-like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient-derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP-induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
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