Hmob2 Deficiency Impairs Homologous Recombination-Mediated Dna Repair And Sensitises Cancer Cells To Parp Inhibitors
| العنوان: | Hmob2 Deficiency Impairs Homologous Recombination-Mediated Dna Repair And Sensitises Cancer Cells To Parp Inhibitors |
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| المؤلفون: | Alexander Hergovich, Angeliki Ditsiou, Juan Jose Garcia-Gomez, Fumiko Esashi, Ramazan Gundogdu, Valenti Gomez, Victoria J. Spanswick, M. Kadir Erdogan, John A. Hartley |
| المصدر: | Cellular Signalling |
| بيانات النشر: | Aperta, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | TCGA, The Cancer Genome Atlas, DSB, DNA double-strand break, PARP, poly(ADP-ribose) polymerase, DNA Repair, DNA repair, DNA damage, Poly ADP ribose polymerase, SSB, DNA single-strand break, Biology, Poly(ADP-ribose) Polymerase Inhibitors, IR, Ionising radiation, Article, DDR, DNA damage response, chemistry.chemical_compound, Homologous recombination DNA repair, Cell Line, Tumor, Neoplasms, medicine, ssDNA, single-stranded DNA, Humans, Homologous Recombination, MMC, mitomycin C, NDR, Nuclear Dbf2-related, DNA damage response signalling, MRN, MRE11-RAD50-NBS1, Cancer, Cell Biology, medicine.disease, Personalised PARP inhibitor treatments, NHEJ, non-homologous end-joining, MOB, Mps one binder, RNAi, RNA interference, chemistry, Cancer cell, PARP inhibitor, Cancer research, HR, homologous recombination, Homologous recombination, Mps one binder 2 (MOB2), DNA, DNA Damage |
| الوصف: | 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 DSB-inducing 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. Highlights • hMOB2 promotes homologous recombination (HR) double-strand break (DSB) repair. • hMOB2 is required for the stabilisation of RAD51 on damaged chromatin. • Low hMOB2 levels potentiate the anti-tumour effects of the DNA-damaging agents. • hMOB2 as a predictive biomarker to PARP inhibition and patient stratification. |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::781e7f8fa05bb5c2814bf41145d35d64Test https://aperta.ulakbim.gov.tr/record/232808Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....781e7f8fa05bb5c2814bf41145d35d64 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |