ArticleGenes & development2019
BRN2 suppresses apoptosis, reprograms DNA damage repair, and is associated with a high somatic mutation burden in melanoma.
Article in Genes & development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Resistance to neoadjuvant talazoparib in triple-negative breast cancer by BRN2-induced ATR/STAT3 pathways or SHLD2 subclone expansion.Proceedings of the National Academy of Sciences of the United States of America · 2026Trial
- Controlling gene expression through five zinc finger domains of ZNF18.Protein science : a publication of the Protein Society · 2025Article
- Homeodomain protein PRRX1 anchors the Ku heterodimers at DNA double-strand breaks to promote nonhomologous end-joining.Nucleic acids research · 2025Article
- DNA damage remodels the MITF interactome to increase melanoma genomic instability.Genes & development · 2024Article
- Developmental reprogramming of myometrial stem cells by endocrine disruptor linking to risk of uterine fibroids.Cellular and molecular life sciences : CMLS · 2023Article
- Non-lethal outcomes of engaging regulated cell death pathways in cancer.Nature cancer · 2023Review
- Overexpression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation.Breast cancer research and treatment · 2023Article
- TEAD Proteins Associate With DNA Repair Proteins to Facilitate Cellular Recovery From DNA Damage.Molecular & cellular proteomics : MCP · 2023Article
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- Current understanding of epigenetics role in melanoma treatment and resistance.Cancer cell international · 2022Review
- Article
- The NRF2-dependent transcriptional axis, XRCC5/hTERT drives tumor progression and 5-Fu insensitivity in hepatocellular carcinoma.Molecular therapy oncolytics · 2022Article
- Article
- DNA repair proteins as the targets for paroxetine to induce cytotoxicity in gastric cancer cell AGS.American journal of cancer research · 2022Article
- BRN2 is a non-canonical melanoma tumor-suppressor.Nature communications · 2021Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression.Neoplasia (New York, N.Y.) · 2021Article
- G-quadruplexes: a promising target for cancer therapy.Molecular cancer · 2021Review
- Transcriptional regulators and alterations that drive melanoma initiation and progression.Oncogene · 2020Review
- BRN2 expression increases anoikis resistance in melanoma.Oncogenesis · 2020Article
Corrections and comments
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Authors and funding
18 authors at 9 institutions in 6 countries.
Funding
Abstract
Whether cell types exposed to a high level of environmental insults possess cell type-specific prosurvival mechanisms or enhanced DNA damage repair capacity is not well understood. BRN2 is a tissue-restricted POU domain transcription factor implicated in neural development and several cancers. In melanoma, BRN2 plays a key role in promoting invasion and regulating proliferation. Here we found, surprisingly, that rather than interacting with transcription cofactors, BRN2 is instead associated with DNA damage response proteins and directly binds PARP1 and Ku70/Ku80. Rapid PARP1-dependent BRN2 association with sites of DNA damage facilitates recruitment of Ku80 and reprograms DNA damage repair by promoting Ku-dependent nonhomologous end-joining (NHEJ) at the expense of homologous recombination. BRN2 also suppresses an apoptosis-associated gene expression program to protect against UVB-, chemotherapy- and vemurafenib-induced apoptosis. Remarkably, BRN2 expression also correlates with a high single-nucleotide variation prevalence in human melanomas. By promoting error-prone DNA damage repair via NHEJ and suppressing apoptosis of damaged cells, our results suggest that BRN2 contributes to the generation of melanomas with a high mutation burden. Our findings highlight a novel role for a key transcription factor in reprogramming DNA damage repair and suggest that BRN2 may impact the response to DNA-damaging agents in BRN2-expressing cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.