Dergi makalesi Açık Erişim
Gundogdu, Ramazan; Erdogan, M. Kadir; Ditsiou, Angeliki; Spanswick, Victoria; Garcia-Gomez, Juan Jose; Hartley, John A.; Esashi, Fumiko; Hergovich, Alexander; Gomez, Valenti
{ "DOI": "10.1016/j.cellsig.2021.110106", "abstract": "Monopolar spindle-one binder (MOBs) proteins are evolutionarily conserved and contribute to various cellular signalling pathways. Recently, we reported that hMOB2 functions in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest in untransformed cells. However, the question of how hMOB2 protects cells from endogenous DNA damage accumulation remained enigmatic. Here, we uncover hMOB2 as a regulator of double-strand break (DSB) repair by homologous recombination (HR). hMOB2 supports the phosphorylation and accumulation of the RAD51 recombinase on resected single-strand DNA (ssDNA) overhangs. Physiologically, hMOB2 expression supports cancer cell survival in response to DSBinducing anti-cancer compounds. Specifically, loss of hMOB2 renders ovarian and other cancer cells more vulnerable to FDA-approved PARP inhibitors. Reduced MOB2 expression correlates with increased overall survival in patients suffering from ovarian carcinoma. Taken together, our findings suggest that hMOB2 expression may serve as a candidate stratification biomarker of patients for HR-deficiency targeted cancer therapies, such as PARP inhibitor treatments.", "author": [ { "family": "Gundogdu", "given": " Ramazan" }, { "family": "Erdogan", "given": " M. Kadir" }, { "family": "Ditsiou", "given": " Angeliki" }, { "family": "Spanswick", "given": " Victoria" }, { "family": "Garcia-Gomez", "given": " Juan Jose" }, { "family": "Hartley", "given": " John A." }, { "family": "Esashi", "given": " Fumiko" }, { "family": "Hergovich", "given": " Alexander" }, { "family": "Gomez", "given": " Valenti" } ], "container_title": "CELLULAR SIGNALLING", "id": "232808", "issued": { "date-parts": [ [ 2021, 1, 1 ] ] }, "title": "hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors", "type": "article-journal", "volume": "87" }
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