Gene of the Month – March: EDC4

An important role of the EDC4 gene in the intricate network regulating the repair of DNA damage and in cancer development has now been uncovered. In a study recently published in Nature Communications, international researchers have elucidated this previously unknown additional function of EDC4 (enhancer of mRNA decapping 4), an RNA degradation enzyme that is involved in removing the protective caps of mRNA in the p-bodies of the cytoplasm. They showed that EDC4 acts in a protein complex with BRCA1, BRIP1 and TOPBP1 in the homologous recombination pathway to repair DNA double strand breaks.

Germline mutations of BRCA1 confer an increased risk of breast and ovarian cancer, and BRCA1-mutated tumors are sensitive to treatment with PARP inhibitors. In genetic and functional analyses, the researchers have now identified dominant EDC4 mutations in BRCA1/2 mutation-negative families and patients with familial breast cancer and they demonstrated that the EDC4 deficiency caused by these mutations leads to genomic instability and increased sensitivity to PARP inhibitors. These findings may thus provide the basis for further research on EDC4 as a tumor suppressor and its potential use as a molecular target in the treatment of cancer.

Hernández G, Ramírez MJ, Minguillón J, […] Surrallés J. Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1. Nat Commun. 2018 Mar 6;9(1):967. doi: 10.1038/s41467-018-03433-3.

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