ArticleMolecular and cellular biology2017
MCL-1 Depletion Impairs DNA Double-Strand Break Repair and Reinitiation of Stalled DNA Replication Forks.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Host mitochondrial apoptotic signatures in children with chronic conditions reveal viral modulation of MCL-1 in severe SARS-CoV-2 infection.Molecular biology reports · 2026Article
- HP1β recruits RING1A to ubiquitinate histone H2A for BRCA1-mediated resection of double-stand breaks.iScience · 2026Article
- Plasma miR-134-5p: a candidate biomarker for predicting non-response to anti-TNF therapy in rheumatoid arthritis.Frontiers in immunology · 2026Observational
- GX15-070 enhances niraparib efficacy in ovarian cancer by promoting a shift in Mcl1-mediated DNA repair pathway from HR to NHEJ.Journal of translational medicine · 2025Article
- MCL1 may not mediate chemoresistance.bioRxiv : the preprint server for biology · 2025Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Mcl-1 deficiency in murine livers leads to nuclear polyploidisation and mitotic errors: Implications for hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2023Article
- Myeloid Cell Leukemia 1 Small Molecule Inhibitor S63845 Synergizes with Cisplatin in Triple-Negative Breast Cancer.Cancers · 2023Article
- Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents.Cancer treatment and research · 2023Review
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- Targeting cancer stemness mediated by BMI1 and MCL1 for non-small cell lung cancer treatment.Journal of cellular and molecular medicine · 2022Article
- Specific Targeting of Antiapoptotic Bcl-2 Proteins as a Radiosensitizing Approach in Solid Tumors.International journal of molecular sciences · 2022Article
- Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis.Oncogene · 2022Article
- Review
- RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair.International journal of molecular sciences · 2021Review
- The multiple mechanisms of MCL1 in the regulation of cell fate.Communications biology · 2021Review
- Article
- Autism-Associated Vigilin Depletion Impairs DNA Damage Repair.Molecular and cellular biology · 2021Article
- Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells.Cells · 2021Article
- Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression.PloS one · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Myeloid cell leukemia 1 (MCL-1) is a prosurvival BCL-2 protein family member highly expressed in hematopoietic stem cells (HSCs) and regulated by growth factor signals that manifest antiapoptotic activity. Here we report that depletion of MCL-1 but not its isoform MCL-1S increases genomic instability and cell sensitivity to ionizing radiation (IR)-induced death. MCL-1 association with genomic DNA increased postirradiation, and the protein colocalized with 53BP1 foci. Postirradiation, MCL-1-depleted cells exhibited decreased γ-H2AX foci, decreased phosphorylation of ATR, and higher levels of residual 53BP1 and RIF1 foci, suggesting that DNA double-strand break (DSB) repair by homologous recombination (HR) was compromised. Consistent with this model, MCL-1-depleted cells had a reduced frequency of IR-induced BRCA1, RPA, and Rad51 focus formation, decreased DNA end resection, and decreased HR repair in the DR-GFP DSB repair model. Similarly, after HU induction of stalled replication forks in MCL-1-depleted cells, there was a decreased ability to subsequently restart DNA synthesis, which is normally dependent upon HR-mediated resolution of collapsed forks. Therefore, the present data support a model whereby MCL-1 depletion increases 53BP1 and RIF1 colocalization at DSBs, which inhibits BRCA1 recruitment, and sensitizes cells to DSBs from IR or stalled replication forks that require HR for repair.
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Registered trials
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