{"doi":"10.1101/2022.01.17.476609","title":"<i>In vivo</i>\n                  inactivation of RAD51-mediated homologous recombination leads to premature aging, but not to tumorigenesis","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Genetic instability is a hallmark of both cancer and aging. Homologous recombination (HR) is a prominent DNA repair pathway maintaining genomic integrity. Mutations in many HR genes lead to cancer predisposition. Paradoxically, the consequences of mutations in the pivotal HR player,\n                  <jats:italic>RAD51</jats:italic>\n                  , on cancer development remain puzzling. Moreover, in contrast with other HR genes, RAD51 mouse models are not available to experimentally address the role of RAD51 on aging and carcinogenesis,\n                  <jats:italic>in vivo</jats:italic>\n                  . Here, we engineered a mouse model with an inducible dominant negative form of RAD51 (\n                  <jats:italic>SMRad51</jats:italic>\n                  ) that suppresses RAD51-mediated HR without stimulating alternative non-conservative repair pathways. We found that,\n                  <jats:italic>in vivo</jats:italic>\n                  expression of\n                  <jats:italic>SMRad51</jats:italic>\n                  did not trigger tumorigenesis, but instead induced premature aging. We propose that these\n                  <jats:italic>in vivo</jats:italic>\n                  phenotypes result from the exhaustion of proliferating progenitors submitted to chronic endogenous replication stress resulting from RAD51-mediated HR suppression. Our data underline the importance of the RAD51 activity for progenitors homeostasis, preventing aging, and more generally for the balance between cancer and aging.\n                </jats:p>","journal":null,"year":null,"id":42154,"datarank":0.14549330712619496,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.041521230042203164,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.041521230042203164,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":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":202160,"name":"Vilma Barroca","orcid":null,"position":1,"is_corresponding":false},{"id":202161,"name":"Ali-Akbar Muhammad","orcid":null,"position":2,"is_corresponding":false},{"id":202162,"name":"Awatef Allouch","orcid":null,"position":3,"is_corresponding":false},{"id":202163,"name":"Stephane Koundrioukoff","orcid":null,"position":4,"is_corresponding":false},{"id":202164,"name":"Daniel Lewandowski","orcid":null,"position":5,"is_corresponding":false},{"id":202165,"name":"Emmanuelle Despras","orcid":null,"position":6,"is_corresponding":false},{"id":202166,"name":"Josée Guirouilh-Barbat","orcid":null,"position":7,"is_corresponding":false},{"id":202167,"name":"Lucien Frappart","orcid":null,"position":8,"is_corresponding":false},{"id":202168,"name":"Patricia Kannouche","orcid":null,"position":9,"is_corresponding":false},{"id":202169,"name":"Pauline Dupaigne","orcid":null,"position":10,"is_corresponding":false},{"id":202170,"name":"Eric Le Cam","orcid":null,"position":11,"is_corresponding":false},{"id":202171,"name":"Jean-Luc Perfettini","orcid":null,"position":12,"is_corresponding":false},{"id":202172,"name":"Paul-Henri Romeo","orcid":null,"position":13,"is_corresponding":false},{"id":202173,"name":"Michelle Debatisse","orcid":null,"position":14,"is_corresponding":false},{"id":120187,"name":"Maria Jasin","orcid":null,"position":15,"is_corresponding":false},{"id":202174,"name":"Gabriel Livera","orcid":null,"position":16,"is_corresponding":false},{"id":202175,"name":"Emmanuelle Martini","orcid":null,"position":17,"is_corresponding":false},{"id":202176,"name":"Bernard S. Lopez","orcid":"0000-0001-5088-0155","position":18,"is_corresponding":false},{"id":202159,"name":"Gabriel Matos-Rodrigues","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18998881","pmcid":null,"openalex_id":"https://openalex.org/W4205933682","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2023,"count":1}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/01/17/2022.01.17.476609.full.pdf","host_type":"repository"},{"url":"https://hal.science/hal-03860785/file/2022.01.17.476609v1.full.pdf","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/01/17/2022.01.17.476609.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2022.01.17.476609","host_type":"publisher"},{"url":"https://doi.org/10.1101/2022.01.17.476609","host_type":"repository"},{"url":"https://hal.science/hal-03853667","host_type":"repository"},{"url":"https://hal.science/hal-03860785","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","PARP inhibition in cancer therapy","CRISPR and Genetic Engineering","Biology","Medicine"],"mesh_terms":[],"keywords":["RAD51","Genome instability","Carcinogenesis","Homologous recombination","DNA repair","Biology","DNA damage","Cancer research","Premature aging","Mutation","Progenitor cell","Cell biology","In vivo","Cancer","Progenitor","Genetics","Gene","DNA","Stem cell"],"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":"2026-06-13T20:49:16.419039Z","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":[]}