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Targeting BRCA-mutated tumors in mitosis

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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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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Correspondence to Shan Zha.

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Menolfi, D., Zha, S. Targeting BRCA-mutated tumors in mitosis. Nat Cancer 2, 1296–1297 (2021).

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