{"doi":"10.1093/nar/gkae239","title":"HELLS regulates transcription in T-cell lymphomas by reducing unscheduled R-loops and by facilitating RNAPII progression","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Chromatin modifiers are emerging as major determinants of many types of cancers, including Anaplastic Large Cell Lymphomas (ALCL), a family of highly heterogeneous T-cell lymphomas for which therapeutic options are still limited. HELLS is a multifunctional chromatin remodeling protein that affects genomic instability by participating in the DNA damage response. Although the transcriptional function of HELLS has been suggested, no clues on how HELLS controls transcription are currently available. In this study, by integrating different multi-omics and functional approaches, we characterized the transcriptional landscape of HELLS in ALCL. We explored the clinical impact of its transcriptional program in a large cohort of 44 patients with ALCL. We demonstrated that HELLS, loaded at the level of intronic regions of target promoters, facilitates RNA Polymerase II (RNAPII) progression along the gene bodies by reducing the persistence of co-transcriptional R-loops and promoting DNA damage resolution. Importantly, selective knockdown of HELLS sensitizes ALCL cells to different chemotherapeutic agents, showing a synergistic effect. Collectively, our work unveils the role of HELLS in acting as a gatekeeper of ALCL genome stability providing a rationale for drug design.</jats:p>","journal":"Nucleic Acids Research","year":2024,"id":608876,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1564316,"name":"Selene Mallia","orcid":null,"position":1,"is_corresponding":false},{"id":1414561,"name":"Veronica Manicardi","orcid":"0000-0003-2490-7283","position":2,"is_corresponding":false},{"id":1414564,"name":"Benedetta Donati","orcid":"0000-0002-9163-8194","position":3,"is_corresponding":false},{"id":1414563,"name":"Federica Torricelli","orcid":"0000-0003-1954-5695","position":4,"is_corresponding":false},{"id":1169698,"name":"Emanuele Vitale","orcid":"0000-0003-1866-2101","position":5,"is_corresponding":false},{"id":580392,"name":"Elisa Salviato","orcid":"0000-0003-3246-7820","position":6,"is_corresponding":false},{"id":1564319,"name":"Giulia Gambarelli","orcid":null,"position":7,"is_corresponding":false},{"id":1414562,"name":"Silvia Muccioli","orcid":"0000-0002-0544-6808","position":8,"is_corresponding":false},{"id":1564321,"name":"Magda Zanelli","orcid":null,"position":9,"is_corresponding":false},{"id":1564322,"name":"Stefano Ascani","orcid":null,"position":10,"is_corresponding":false},{"id":530786,"name":"Giovanni Martino","orcid":"0000-0003-2202-257X","position":11,"is_corresponding":false},{"id":1026718,"name":"Francesca Sanguedolce","orcid":"0000-0001-7459-3521","position":12,"is_corresponding":false},{"id":1564324,"name":"Elisabetta Sauta","orcid":null,"position":13,"is_corresponding":false},{"id":1564325,"name":"Ione Tamagnini","orcid":null,"position":14,"is_corresponding":false},{"id":1564326,"name":"Noemi Puccio","orcid":null,"position":15,"is_corresponding":false},{"id":763581,"name":"Antonino Neri","orcid":"0000-0001-9047-5912","position":16,"is_corresponding":false},{"id":1414571,"name":"Alessia Ciarrocchi","orcid":"0000-0002-5541-2075","position":17,"is_corresponding":false},{"id":1564328,"name":"Valentina Fragliasso","orcid":"0000-0002-4189-0316","position":18,"is_corresponding":false},{"id":1564315,"name":"Annalisa Tameni","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"HELLS regulates transcription in T-cell lymphomas by reducing unscheduled R-loops and by facilitating RNAPII progression","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Chromatin modifiers are emerging as major determinants of many types of cancers, including Anaplastic Large Cell Lymphomas (ALCL), a family of highly heterogeneous T-cell lymphomas for which therapeutic options are still limited. HELLS is a multifunctional chromatin remodeling protein that affects genomic instability by participating in the DNA damage response. Although the transcriptional function of HELLS has been suggested, no clues on how HELLS controls transcription are currently available. In this study, by integrating different multi-omics and functional approaches, we characterized the transcriptional landscape of HELLS in ALCL. We explored the clinical impact of its transcriptional program in a large cohort of 44 patients with ALCL. We demonstrated that HELLS, loaded at the level of intronic regions of target promoters, facilitates RNA Polymerase II (RNAPII) progression along the gene bodies by reducing the persistence of co-transcriptional R-loops and promoting DNA damage resolution. Importantly, selective knockdown of HELLS sensitizes ALCL cells to different chemotherapeutic agents, showing a synergistic effect. Collectively, our work unveils the role of HELLS in acting as a gatekeeper of ALCL genome stability providing a rationale for drug design.</jats:p>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38597676","pmcid":"PMC11194065","openalex_id":"https://openalex.org/W4394675071","authors":[],"funders":[{"funder_name":"Fondazione AIRC per la Ricerca sul Cancro","grant_id":"MFAG 2023","title":null},{"funder_name":"Fondazione GRADE Onlus","grant_id":"","title":null},{"funder_name":"Fondazione AIRC per la Ricerca sul Cancro","grant_id":"","title":null},{"funder_name":"Bando per la Valorizzazione della Ricerca Istituzionale 2021-fondi 5 per Mille 2020","grant_id":"","title":null},{"funder_name":"Fondazione AIACE","grant_id":"","title":null},{"funder_name":"Fondazione Guido Berlucchi","grant_id":"","title":null},{"funder_name":"Italian Ministry of Health-Ricerca Corrente Annual Program 2025","grant_id":"","title":null},{"funder_name":"Fondazione AIRC per la Ricerca sul Cancro","grant_id":"","title":null},{"funder_name":"Fondazione GRADE Onlus","grant_id":"","title":null},{"funder_name":"Fondazione Guido Berlucchi","grant_id":"","title":null},{"funder_name":"Bando per la Valorizzazione della Ricerca Istituzionale 2021-fondi 5 per Mille 2020","grant_id":"","title":null},{"funder_name":"Fondazione AIACE","grant_id":"","title":null},{"funder_name":"Italian Ministry of Health-Ricerca Corrente Annual Program 2025","grant_id":"","title":null}],"total_grants":13,"fwci":1.4646,"citation_percentile":0.80883386,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkae239/57199767/gkae239.pdf","host_type":"journal"},{"url":"https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkae239/57199767/gkae239.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/nar/article-pdf/52/11/6171/58306664/gkae239.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/nar/gkae239","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38597676","host_type":"repository"},{"url":"https://hdl.handle.net/11380/1352726","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11194065","host_type":"repository"},{"url":"https://hdl.handle.net/11380/1384988","host_type":"repository"},{"url":"https://hdl.handle.net/11380/1386851","host_type":"repository"},{"url":"https://iris.unimore.it/bitstream/11380/1352726/1/gkae239.pdf","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11194065/pdf/gkae239.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11194065","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11194065?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Genomics and Chromatin Dynamics","T-cell and Retrovirus Studies","Lymphoma Diagnosis and Treatment","Humans","RNA Polymerase II","R-Loop Structures","Transcription, Genetic","DNA Damage","Cell Line, Tumor","Genomic Instability","Lymphoma, Large-Cell, Anaplastic","Gene Expression Regulation, Neoplastic","DNA Helicases","Promoter Regions, Genetic","Lymphoma, T-Cell"],"mesh_terms":["R-Loop Structures","DNA Damage","DNA Helicases","Humans","Promoter Regions, Genetic","RNA Polymerase II","Transcription, Genetic","Gene Expression Regulation, Neoplastic","Lymphoma, T-Cell","Lymphoma, Large-Cell, Anaplastic","Genomic Instability","Cell Line, Tumor"],"keywords":["Biology","Chromatin","DNA damage","Transcription (linguistics)","Genome instability","Gene knockdown","Cancer research","Promoter","RNA polymerase II","DNA repair","Gene","DNA","Cell biology","Genetics","Gene expression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T23:36:43.971437Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}