ArticleProceedings of the National Academy of Sciences of the United States of America2015
BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 43 citations in OpenAlex.
- A Novel BIRC6 Variant Impairs Apoptotic Regulation in Familial Premature Ovarian Insufficiency: Functional Validation in a CRISPR/Cas9 Zebrafish Model.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- The IAP family member BRUCE/BIRC6: an emerging new player in balancing life and death.Apoptosis : an international journal on programmed cell death · 2026Review
- Deubiquitinase USP8 regulates the spindle assembly checkpoint in oocytes.Science advances · 2026Article
- BRUCE liver-KO enhances MASLD/MASH development in the steatotic PTEN-KO background by impairing mitochondrial metabolism and activating STAT3.Cell death & disease · 2025Article
- Article
- Elucidation of short linear motif-based interactions of the MIT and rhodanese domains of the ubiquitin-specific protease 8.Biology direct · 2025Article
- YTHDC1 mThe EMBO journal · 2024Article
- Microcephaly GeneInternational journal of molecular sciences · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes.Communications biology · 2023Article
- USP8 inhibitor-induced DNA damage activates cell cycle arrest, apoptosis, and autophagy in esophageal squamous cell carcinoma.Cell biology and toxicology · 2023Article
- Deubiquitination complex platform: A plausible mechanism for regulating the substrate specificity of deubiquitinating enzymes.Acta pharmaceutica Sinica. B · 2023Review
- The expanded inhibitor of apoptosis gene family in oysters possesses novel domain architectures and may play diverse roles in apoptosis following immune challenge.BMC genomics · 2022Article
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Bacterial Genotoxin Accelerates Transient Infection-Driven Murine Colon Tumorigenesis.Cancer discovery · 2022Article
- Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response.The Journal of biological chemistry · 2021Review
- BIR repeat-containing ubiquitin conjugating enzyme (BRUCE) regulation of β-catenin signaling in the progression of drug-induced hepatic fibrosis and carcinogenesis.World journal of hepatology · 2021Article
- Review
- Ubiquitin-specific peptidase 8 regulates the trafficking and stability of the human organic anion transporter 1.Biochimica et biophysica acta. General subjects · 2020Article
- Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.Molecular cell · 2020Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The DNA damage response (DDR) is crucial for genomic integrity. BRIT1 (breast cancer susceptibility gene C terminus-repeat inhibitor of human telomerase repeat transcriptase expression), a tumor suppressor and early DDR factor, is recruited to DNA double-strand breaks (DSBs) by phosphorylated H2A histone family, member X (γ-H2AX), where it promotes chromatin relaxation by recruiting the switch/sucrose nonfermentable (SWI-SNF) chromatin remodeler to facilitate DDR. However, regulation of BRIT1 recruitment is not fully understood. The baculovirus IAP repeat (BIR)-containing ubiquitin-conjugating enzyme (BRUCE) is an inhibitor of apoptosis protein (IAP). Here, we report a non-IAP function of BRUCE in the regulation of the BRIT1-SWI-SNF DSB-response pathway and genomic stability. We demonstrate that BRIT1 is K63 ubiquitinated in unstimulated cells and that deubiquitination of BRIT1 is a prerequisite for its recruitment to DSB sites by γ-H2AX. We show mechanistically that BRUCE acts as a scaffold, bridging the ubiquitin-specific peptidase 8 (USP8) and BRIT1 in a complex to coordinate USP8-catalyzed deubiquitination of BRIT1. Loss of BRUCE or USP8 impairs BRIT1 deubiquitination, BRIT1 binding with γ-H2AX, the formation of BRIT1 DNA damage foci, and chromatin relaxation. Moreover, BRUCE-depleted cells display reduced homologous recombination repair, and BRUCE-mutant mice exhibit repair defects and genomic instability. These findings identify BRUCE and USP8 as two hitherto uncharacterized critical DDR regulators and uncover a deubiquitination regulation of BRIT1 assembly at damaged chromatin for efficient DDR and genomic stability.
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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.