{"doi":"10.64898/2026.01.30.702603","title":"The glycine-arginine-rich motif of 53BP1 modulates RNA interactions necessary for its liquid-liquid phase separation during DNA Damage Response","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  The DNA damage response relies on the rapid assembly of repair factors into foci with properties of liquid-liquid phase separation, driven by\n                  <jats:italic>de novo</jats:italic>\n                  transcription of damage-induced RNAs. 53BP1 is a key component of these condensates, yet the molecular determinants driving this process remain unknown. Here, through computational, structural and\n                  <jats:italic>in vitro</jats:italic>\n                  approaches, we identify the oligomerization domain of 53BP1 and its glycine-arginine-rich (GAR) motif as crucial for RNA interactions and phase separation. Biophysical characterization reveals that 53BP1-RNA condensates can progressively mature into a more stable state, and that GAR mutants display aberrant material properties. Using a cellular model of telomere fusion events, we demonstrate that the GAR motif is essential for 53BP1-mediated DNA repair, which depends on the combined contributions of RNA binding and appropriate condensate biophysical properties. Therefore, RNA-driven 53BP1 condensation is functionally required to maintain genome integrity.\n                </jats:p>","journal":null,"year":null,"id":648878,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"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":1691294,"name":"Marta Ceccon","orcid":"0000-0002-4815-889X","position":1,"is_corresponding":false},{"id":1691296,"name":"Oscar Sapkota","orcid":"0000-0002-7286-8808","position":2,"is_corresponding":false},{"id":691097,"name":"Tongyin Zheng","orcid":"0000-0002-5132-6436","position":3,"is_corresponding":false},{"id":1691299,"name":"Matteo Brizioli","orcid":"0000-0001-5470-3017","position":4,"is_corresponding":false},{"id":1691302,"name":"Angela dello Stritto","orcid":"0000-0001-9469-6122","position":5,"is_corresponding":false},{"id":1691304,"name":"Samara Cummings","orcid":"0009-0003-7605-4099","position":6,"is_corresponding":false},{"id":1691305,"name":"Simone Codispoti","orcid":"0009-0003-9374-3865","position":7,"is_corresponding":false},{"id":1691307,"name":"Giuseppe Ossolengo","orcid":null,"position":8,"is_corresponding":false},{"id":1691309,"name":"Fabrizio Orsenigo","orcid":"0000-0001-9135-8478","position":9,"is_corresponding":false},{"id":1691311,"name":"Serena Magni","orcid":"0000-0003-4730-9710","position":10,"is_corresponding":false},{"id":1691313,"name":"Andrea Gottinger","orcid":"0000-0002-0859-5569","position":11,"is_corresponding":false},{"id":6644,"name":"Andrea Mattevi","orcid":"0000-0002-9523-7128","position":12,"is_corresponding":false},{"id":1361282,"name":"Mónika Fuxreiter","orcid":"0000-0002-4463-6727","position":13,"is_corresponding":false},{"id":303973,"name":"Nicolas L. Fawzi","orcid":"0000-0001-5483-0577","position":14,"is_corresponding":false},{"id":1036153,"name":"Francisca Lottersberger","orcid":"0000-0002-0677-8986","position":15,"is_corresponding":false},{"id":1116214,"name":"Fabio Giavazzi","orcid":"0000-0003-4930-0592","position":16,"is_corresponding":false},{"id":681641,"name":"Fabrizio d’Adda di Fagagna","orcid":"0000-0002-9603-5966","position":17,"is_corresponding":false},{"id":1691293,"name":"Federica Terraneo","orcid":"0000-0001-6161-1583","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The glycine-arginine-rich motif of 53BP1 modulates RNA interactions necessary for its liquid-liquid phase separation during DNA Damage Response","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  The DNA damage response relies on the rapid assembly of repair factors into foci with properties of liquid-liquid phase separation, driven by\n                  <jats:italic>de novo</jats:italic>\n                  transcription of damage-induced RNAs. 53BP1 is a key component of these condensates, yet the molecular determinants driving this process remain unknown. Here, through computational, structural and\n                  <jats:italic>in vitro</jats:italic>\n                  approaches, we identify the oligomerization domain of 53BP1 and its glycine-arginine-rich (GAR) motif as crucial for RNA interactions and phase separation. Biophysical characterization reveals that 53BP1-RNA condensates can progressively mature into a more stable state, and that GAR mutants display aberrant material properties. Using a cellular model of telomere fusion events, we demonstrate that the GAR motif is essential for 53BP1-mediated DNA repair, which depends on the combined contributions of RNA binding and appropriate condensate biophysical properties. Therefore, RNA-driven 53BP1 condensation is functionally required to maintain genome integrity.\n                </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19965766","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://syndication.highwire.org/content/doi/10.64898/2026.01.30.702603","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T03:05:17.245678Z","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":[]}