Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS/AML.

doi:10.1172/jci.insight.142149

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Article

Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS/AML.

JCI insight - 8 Feb 2021

Tothova Zuzana, Valton Anne-Laure, Gorelov Rebecca A, Vallurupalli Mounica, Krill-Burger John M, Holmes Amie, Landers Catherine C, Haydu J Erika, Malolepsza Edyta, Hartigan Christina, Donahue Melanie, Popova Katerina D, Koochaki Sebastian, Venev Sergey V, Rivera Jeanne, Chen Edwin, Lage Kasper, Schenone Monica, D'Andrea Alan D, Carr Steven A, Morgan Elizabeth A, Dekker Job, Ebert Benjamin L

Abstract excerpt

The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair and replication as genetic...

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PMID: 33351783
DOI: 10.1172/jci.insight.142149
PMCID: PMC7934867

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