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Omics score: 0

A non-catalytic function of SETD1A regulates Cyclin K and the DNA damage response

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

OTHER RELATED OMICS DATASETS IN: MSV000080012

ORGANISM(S): Mus musculus

PROVIDER: GSE108615 | GEO | 2018/02/01

REPOSITORIES: GEO

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A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response.

Project description: Not available

| S-EPMC6052445 | biostudies-literature

A non-catalytic function of SETD1A regulates Cyclin K and the DNA damage response [RNA-seq]

Project description:MLL/SET methyltransferases catalyze methylation of histone 3 lysine 4 and play critical roles in development and cancer. We assessed MLL/SET proteins and found that SETD1A is required for survival of acute myeloid leukemia (AML) cells. Mutagenesis studies and CRISPR-Cas9 domain screening, showed the enzymatic SET domain is not necessary for AML cell survival but that a newly identified region, termed the FLOS (Functional Location on SETD1A) domain, is indispensable. FLOS disruption suppresses DNA damage response genes and induces p53-dependent apoptosis. The FLOS domain acts as a Cyclin K-binding site that is required for chromosomal recruitment of Cyclin K, and for DNA repair-associated gene expression in S phase. These data identify a connection between the chromatin regulator SETD1A and the DNA damage response that is independent of histone methylation, and suggests that targeting SETD1A and Cyclin K complexes may represent a therapeutic opportunity for AML and potentially other cancers.

2018-02-01 | GSE108614 | GEO