{"doi":"10.1016/j.celrep.2025.116094","title":"Leishmania major chromosomes are replicated from a single high-efficiency locus supplemented by thousands of lower efficiency initiation events","abstract":null,"journal":"Cell Reports","year":2025,"id":682190,"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":1782225,"name":"Gabriel L.A. Silva","orcid":null,"position":1,"is_corresponding":false},{"id":1782226,"name":"Catarina A. Marques","orcid":null,"position":2,"is_corresponding":false},{"id":1782227,"name":"Marija Krasilnikova","orcid":null,"position":3,"is_corresponding":false},{"id":1782228,"name":"Craig Lapsley","orcid":null,"position":4,"is_corresponding":false},{"id":252103,"name":"Dario Beraldi","orcid":"0000-0003-1504-5212","position":5,"is_corresponding":false},{"id":1569027,"name":"Richard McCulloch","orcid":"0000-0001-5739-976X","position":6,"is_corresponding":false},{"id":1782224,"name":"Jeziel D. Damasceno","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Leishmania major chromosomes are replicated from a single high-efficiency locus supplemented by thousands of lower efficiency initiation events","abstract":"DNA replication initiates at genome sites termed origins. Previous origin mapping approaches in the populations of the protozoan parasite Leishmania major were discordant, suggesting either a single origin per chromosome or 200-fold more origins. To reconcile these data and fully understand DNA replication dynamics, we have applied DNAscent, an assay that detects patterns of 5-bromodeoxyuridine (BrdU) incorporation in individual long-read DNA molecules. We confirm the pre-eminence of a single locus of DNA replication initiation in each chromosome and reveal a much larger number of lower-efficiency DNA replication initiation events whose abundance is greater as chromosome size increases. Each initiation site is a region of high AT content, increased G-quadruplex levels, lowered chromatin occupancy, and reduced levels of nascent RNA. Finally, we show that all DNA replication initiation results in mutagenesis. This work reveals a bimodal strategy for DNA replication programming in Leishmania that drives replication timing and sequence variation.","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":"40768333","pmcid":"PMC12890776","openalex_id":"https://openalex.org/W4412982400","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"224501/Z/21/Z","title":null},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/W001101/1","title":"A distinct mode of DNA replication initiation in trypanosomes?"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/N016165/1","title":"How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites?"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/R017166/1","title":"Does genome replication in Leishmania rely on origin-independent initiation?"},{"funder_name":"EU Framework Programme for Research and Innovation Marie Skłodowska-Curie Actions","grant_id":"750259","title":"Recombination-derived replication in the eukaryotic microbe Leishmania: a genome-wide process?"},{"funder_name":"UK Research and Innovation Medical Research Council","grant_id":"MR/S019472/1","title":"UK:Brazil Joint Centre Partnership in leishmaniasis"},{"funder_name":"Horizon 2020 Framework Programme","grant_id":"104111","title":null}],"total_grants":7,"fwci":1.1682,"citation_percentile":0.77891899,"influential_citations":0,"citation_trend":[{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.cell.com/cell-reports/pdf/S2211-1247(25)00865-4.pdf","host_type":"journal"},{"url":"https://www.cell.com/cell-reports/pdf/S2211-1247(25)00865-4.pdf","host_type":"GOLD"},{"url":"https://www.cell.com/cell-reports/pdf/S2211-1247(25)00865-4.pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211124725008654?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211124725008654?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.celrep.2025.116094","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40768333","host_type":"repository"},{"url":"https://eprints.gla.ac.uk/view/author/32546.html>","host_type":"journal"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12890776","host_type":"repository"},{"url":"https://doaj.org/article/bd3dcf57b2894356b9c10dc21b38a69a","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12890776/","host_type":"repository"},{"url":"https://eprints.gla.ac.uk/359981/1/359981.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12890776","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12890776?pdf=render","host_type":"Europe_PMC"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40768333/","host_type":""}],"fields_of_study":["DNA and Nucleic Acid Chemistry","HIV/AIDS drug development and treatment","DNA Repair Mechanisms","Medicine","Biology","0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Chromatin","Chromosomes","DNA Replication","Leishmania major","Replication Origin","G-Quadruplexes","Genetic Loci"],"keywords":["Locus (genetics)","Biology","Genetics","Computational biology","Gene","Leishmania","DNA replication","Aneuploidy","Genome Stability","Replication Timing","Genome Plasticity","Long-read Sequencing","Dnascent","Cp: Molecular Biology","Oringins","G-Quadruplexes","Genetic Loci","Replication Origin","Article","Chromosomes","Chromatin","Leishmania major"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T19:42:49.186713Z","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":[]}