{"doi":"10.1101/2020.11.28.401471","title":"Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  In early embryogenesis of fast cleaving embryos DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient implying the possible generation of mutations. We have analyzed mutagenesis in\n                  <jats:italic>Xenopus laevis</jats:italic>\n                  and\n                  <jats:italic>Drosophila melanogaster</jats:italic>\n                  early embryos. We report the occurrence of a high mutation rate in\n                  <jats:italic>Xenopus</jats:italic>\n                  and show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastoderm\n                  <jats:italic>Drosophila</jats:italic>\n                  embryo resulted in reduction of both the hatching rate and Single Nucleotide Variations on specific chromosome regions in adult flies. Altogether, these findings indicate that during very early\n                  <jats:italic>Xenopus</jats:italic>\n                  and\n                  <jats:italic>Drosophila</jats:italic>\n                  embryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.\n                </jats:p>","journal":null,"year":null,"id":650034,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"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":998514,"name":"Isabelle Busseau","orcid":"0000-0001-5194-1298","position":1,"is_corresponding":false},{"id":1694821,"name":"Claudio Lorenzi","orcid":"0000-0002-4208-0403","position":2,"is_corresponding":false},{"id":1694822,"name":"Cima Saghira","orcid":null,"position":3,"is_corresponding":false},{"id":298704,"name":"Matt C. Danzi","orcid":"0000-0003-1568-5965","position":4,"is_corresponding":false},{"id":88911,"name":"Stephan Züchner","orcid":"0000-0002-8498-5235","position":5,"is_corresponding":false},{"id":770298,"name":"Domenico Maiorano","orcid":"0000-0003-4229-5903","position":6,"is_corresponding":false},{"id":1694819,"name":"Elena Lo Furno","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  In early embryogenesis of fast cleaving embryos DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient implying the possible generation of mutations. We have analyzed mutagenesis in\n                  <jats:italic>Xenopus laevis</jats:italic>\n                  and\n                  <jats:italic>Drosophila melanogaster</jats:italic>\n                  early embryos. We report the occurrence of a high mutation rate in\n                  <jats:italic>Xenopus</jats:italic>\n                  and show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastoderm\n                  <jats:italic>Drosophila</jats:italic>\n                  embryo resulted in reduction of both the hatching rate and Single Nucleotide Variations on specific chromosome regions in adult flies. Altogether, these findings indicate that during very early\n                  <jats:italic>Xenopus</jats:italic>\n                  and\n                  <jats:italic>Drosophila</jats:italic>\n                  embryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.\n                </jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W3107641124","authors":[],"funders":[{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-12-BSV2-0022","title":"Regulation of genome stability during embryonic development"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2025,"count":1}],"oa_status":"green","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/06/15/2020.11.28.401471.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/06/15/2020.11.28.401471.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2020.11.28.401471","host_type":"publisher"},{"url":"https://doi.org/10.1101/2020.11.28.401471","host_type":"repository"},{"url":"https://hal.science/hal-03380318","host_type":"repository"},{"url":"https://hal.archives-ouvertes.fr/hal-03380318/file/2020.11.28.401471v4.full.pdf","host_type":""},{"url":"https://dx.doi.org/10.5281/zenodo.4646657","host_type":""},{"url":"https://zenodo.org/records/4646657","host_type":""},{"url":"http://dx.doi.org/10.5281/zenodo.4646657","host_type":""},{"url":"https://dx.doi.org/10.5281/zenodo.4646656","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.11.28.401471","host_type":""}],"fields_of_study":["DNA Repair Mechanisms","Chromosomal and Genetic Variations","Cancer Genomics and Diagnostics","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Biology","Xenopus","Genetics","Embryo","Mutagenesis","Drosophila melanogaster","Blastoderm","Mutation","Cell biology","Embryogenesis","Gene","ubiquitin","nucleus","chromatin","PCNA","Drosophila"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T04:44:07.783455Z","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":[]}