ArticleThe Journal of clinical investigation2019
CDCA7 and HELLS mutations undermine nonhomologous end joining in centromeric instability syndrome.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 99 citations in OpenAlex.
- Functional characterization of UHRF1 variants in facilitating DNA methylation.The Journal of biological chemistry · 2026Article
- Dysregulated HELLS expression alters cellular processes and serves as a potential prognostic marker in acute myeloid leukemia.The Journal of biological chemistry · 2026Article
- CDCA7 targets LSH to DNA maintenance methylation in S phase and transcription regulation in interphase via two distinct DNA-binding modes.Nucleic acids research · 2026Article
- Structure of human lymphoid-specific helicase HELLS in its autoinhibited state.Nucleic acids research · 2026Article
- Missense substitutions in the BTB domain of ZBTB24 can lead to protein instability and cause ICF2 syndrome.Human molecular genetics · 2026Article
- ICF syndrome: An epigenetic paradigm for primary immunodeficiencies.Journal of human immunity · 2026Review
- Structure of human lymphoid-specific helicase HELLS in its autoinhibitory state.bioRxiv : the preprint server for biology · 2025Article
- The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.Nucleic acids research · 2025Article
- The ZBTB24-CDCA7-HELLS axis suppresses the totipotent 2C-like reprogramming by maintaining Dux methylation and repression.Nucleic acids research · 2025Article
- HELLS controls mitochondrial dynamics and genome stability in liver cancer by collusion with MIEF1.Cell death & disease · 2025Article
- ZBTB24 is a conserved multifaceted transcription factor at genes and centromeres that governs the DNA methylation state and expression of satellite repeats.Human molecular genetics · 2025Article
- MiR-335-5p Escaped from CircKIAA0586 Adsorption Contributes to Mechanical Overloading-Induced Cartilage Degeneration by Targeting Lymphoid-Specific Helicase.Research (Washington, D.C.) · 2025Article
- Cellular senescence as a source of chronic microinflammation that promotes the aging process.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- The C-terminal 4CXXC-type zinc finger domain of CDCA7 recognizes hemimethylated DNA and modulates activities of chromatin remodeling enzyme HELLS.Nucleic acids research · 2024Article
- The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cells via promoting heme synthesis.Cellular & molecular biology letters · 2024Article
- The maternal protein NLRP5 stabilizes UHRF1 in the cytoplasm: implication for the pathogenesis of multilocus imprinting disturbance.Human molecular genetics · 2024Article
- Retrotransposon addiction promotes centromere function via epigenetically activated small RNAs.Nature plants · 2024Article
- CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.Science advances · 2024Article
- The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA.Science advances · 2024Article
- HELLS regulates transcription in T-cell lymphomas by reducing unscheduled R-loops and by facilitating RNAPII progression.Nucleic acids research · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutations in CDCA7 and HELLS that respectively encode a CXXC-type zinc finger protein and an SNF2 family chromatin remodeler cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome types 3 and 4. Here, we demonstrate that the classical nonhomologous end joining (C-NHEJ) proteins Ku80 and Ku70, as well as HELLS, coimmunoprecipitated with CDCA7. The coimmunoprecipitation of the repair proteins was sensitive to nuclease treatment and an ICF3 mutation in CDCA7 that impairs its chromatin binding. The functional importance of these interactions was strongly suggested by the compromised C-NHEJ activity and significant delay in Ku80 accumulation at DNA damage sites in CDCA7- and HELLS-deficient HEK293 cells. Consistent with the repair defect, these cells displayed increased apoptosis, abnormal chromosome segregation, aneuploidy, centrosome amplification, and significant accumulation of γH2AX signals. Although less prominent, cells with mutations in the other ICF genes DNMT3B and ZBTB24 (responsible for ICF types 1 and 2, respectively) showed similar defects. Importantly, lymphoblastoid cells from ICF patients shared the same changes detected in the mutant HEK293 cells to varying degrees. Although the C-NHEJ defect alone did not cause CG hypomethylation, CDCA7 and HELLS are involved in maintaining CG methylation at centromeric and pericentromeric repeats. The defect in C-NHEJ may account for some common features of ICF cells, including centromeric instability, abnormal chromosome segregation, and apoptosis.
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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.