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CANCER BIOLOGY

Targeting BRCA-mutated tumors in mitosis

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A genome-wide CRISPR screen finds CIP2A as a new synthetic lethal target for BRCA1- and BRCA2-deficient cells. Unlike PARP inhibition that increases replication-induced DNA double-strand breaks and radial chromosomes, depleting CIP2A or disrupting its interaction with TOPBP1 increases micronuclei and chromosomal missegregation, revealing a mitotic target for BRCA-mutated tumors.

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Fig. 1: BRCA1- and BRCA2-deficient cells accumulate DNA damage and breaks in mitosis probably caused by incomplete chromosome replication, particularly in the absence of TP53.

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Acknowledgements

D.M. was a senior fellow of the Leukemia & Lymphoma Society. The work is in part supported by NIH1R01CA215067 to S.Z.

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Authors and Affiliations

  1. Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Demis Menolfi & Shan Zha

  2. Division of Pediatric Oncology, Hematology and Stem Cell Transplantation, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Shan Zha

Authors
  1. Demis Menolfi
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  2. Shan Zha
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Correspondence to Shan Zha.

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Menolfi, D., Zha, S. Targeting BRCA-mutated tumors in mitosis. Nat Cancer 2, 1296–1297 (2021). https://doi.org/10.1038/s43018-021-00293-7

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