ArticleScience advances2021
ATM-phosphorylated SPOP contributes to 53BP1 exclusion from chromatin during DNA replication.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
40 citing papers in PubMed, 44 citations in OpenAlex.
- Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.Genes & diseases · 2027Review
- Large-scale quaternary structural transitions underlie gain of function of SPOP cancer mutations.Molecular cell · 2026Article
- SPOP-mediated nuclear ubiquitination degradation of p62/SQSTM1 contributes to HR repair.Oncogene · 2026Article
- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- PARG inhibition in ATM-deficient prostate cancer: from mechanistic discovery to therapeutic potential.Journal of translational medicine · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Reduced YTHDF2 inhibits PD-L1 expression by stabilizing mCell death & disease · 2026Article
- Ubiquitin System-Driven Proteostasis in DNA Damage Response.International journal of molecular sciences · 2026Review
- CK2-mediated HDAC5 shuttling regulates DNA end resection through Ku70 deacetylation.Theranostics · 2026Article
- ACSS1 co-opts acetyl-CoA metabolism to drive DNA repair and undermine radiotherapy efficacy in breast cancer.Cell death & disease · 2025Article
- Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity.Cell death & disease · 2025Article
- A structurally informed human protein-protein interactome reveals proteome-wide perturbations caused by disease mutations.Nature biotechnology · 2025Article
- Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment.The Journal of clinical investigation · 2025Article
- In-Cell Approach to Evaluate E3 Ligases for Use in Targeted Protein Degradation.Journal of the American Chemical Society · 2025Article
- The equilibrium between two quaternary assembly states determines the activity of SPOP and its cancer mutants.bioRxiv : the preprint server for biology · 2025Article
- Cullin 3-mediated ubiquitination restricts enterovirus D68 replication and is counteracted by viral protease 3C.Journal of virology · 2025Article
- Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.The Biochemical journal · 2025Article
- SPOP mutations increase PARP inhibitor sensitivity via CK2/PIAS1/SPOP axis in prostate cancer.JCI insight · 2025Article
- Cul3 substrate adaptor SPOP targets Nup153 for degradation.Molecular biology of the cell · 2025Article
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
53BP1 activates nonhomologous end joining (NHEJ) and inhibits homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Dissociation of 53BP1 from DSBs and consequent activation of HR, a less error-prone pathway than NHEJ, helps maintain genome integrity during DNA replication; however, the underlying mechanisms are not fully understood. Here, we demonstrate that E3 ubiquitin ligase SPOP promotes HR during S phase of the cell cycle by excluding 53BP1 from DSBs. In response to DNA damage, ATM kinase-catalyzed phosphorylation of SPOP causes a conformational change in SPOP, revealed by x-ray crystal structures, that stabilizes its interaction with 53BP1. 53BP1-bound SPOP induces polyubiquitination of 53BP1, eliciting 53BP1 extraction from chromatin by a valosin-containing protein/p97 segregase complex. Our work shows that SPOP facilitates HR repair over NHEJ during DNA replication by contributing to 53BP1 removal from chromatin. Cancer-derived SPOP mutations block SPOP interaction with 53BP1, inducing HR defects and chromosomal instability.
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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.