ArticleNature communications2021
The epigenetic regulator LSH maintains fork protection and genomic stability via MacroH2A deposition and RAD51 filament formation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Narciclasine Exerts Anticancer Activity in Colorectal Cancer Cells in Association with HELLS Downregulation and DNA Damage-Associated Responses.Pharmaceuticals (Basel, Switzerland) · 2026Article
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Dysregulated HELLS expression alters cellular processes and serves as a potential prognostic marker in acute myeloid leukemia.The Journal of biological chemistry · 2026Article
- Structure of human lymphoid-specific helicase HELLS in its autoinhibited state.Nucleic acids research · 2026Article
- Photoclick chemistry led to the identification of HELLS as a helicase for DNA G-quadruplexes.Nucleic acids research · 2026Article
- 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
- Ubiquitination of the histone variant mH2A1.2 prevents toxic RAD18 accumulation at a subset of genomic loci upon replication stress.Molecular cell · 2025Article
- Multifunctional histone variants in genome function.Nature reviews. Genetics · 2025Review
- Epigenetic pharmacology in aging: from mechanisms to therapies for age-related disorders.Frontiers in pharmacology · 2025Review
- CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.Science advances · 2024Article
- HELLS regulates transcription in T-cell lymphomas by reducing unscheduled R-loops and by facilitating RNAPII progression.Nucleic acids research · 2024Article
- Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors.Nucleic acids research · 2024Article
- MBD1 protects replication fork stability by recruiting PARP1 and controlling transcription-replication conflicts.Cancer gene therapy · 2024Article
- Coevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases.eLife · 2023Article
- Extrachromosomal circular DNA and structural variants highlight genome instability in Arabidopsis epigenetic mutants.Nature communications · 2023Article
- Coevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases.bioRxiv : the preprint server for biology · 2023Article
- USP11-mediated LSH deubiquitination inhibits ferroptosis in colorectal cancer through epigenetic activation of CYP24A1.Cell death & disease · 2023Article
- Higher-order modular regulation of the human proteome.Molecular systems biology · 2023Article
- Histone H2A variants: Diversifying chromatin to ensure genome integrity.Seminars in cell & developmental biology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
The Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome is caused by mutations in LSH/HELLS, a chromatin remodeler promoting incorporation of histone variant macroH2A. Here, we demonstrate that LSH depletion results in degradation of nascent DNA at stalled replication forks and the generation of genomic instability. The protection of stalled forks is mediated by macroH2A, whose knockdown mimics LSH depletion and whose overexpression rescues nascent DNA degradation. LSH or macroH2A deficiency leads to an impairment of RAD51 loading, a factor that prevents MRE11 and EXO1 mediated nascent DNA degradation. The defect in RAD51 loading is linked to a disbalance of BRCA1 and 53BP1 accumulation at stalled forks. This is associated with perturbed histone modifications, including abnormal H4K20 methylation that is critical for BRCA1 enrichment and 53BP1 exclusion. Altogether, our results illuminate the mechanism underlying a human syndrome and reveal a critical role of LSH mediated chromatin remodeling in genomic stability.
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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.