{"doi":"10.1101/2025.11.03.686349","title":"Comparative analysis of single-stranded and non-canonical DNA formation in human and other ape cells with telomere-to-telomere genomes","abstract":"Summary Non-canonical (non-B) DNA secondary structures, e.g., G-quadruplexes and triplex DNA, are mutation hotspots and genome regulators contributing to disease and evolution. Yet they remain uncharacterized in complete genomes in vivo . Here we exploited the fact that many non-B DNA structures form single-stranded DNA (ssDNA). Using permanganate/S1 footprinting across 14 cell lines, we generated ssDNA profiles for human and six non-human ape telomere-to-telomere (T2T) genomes. Newly resolved satellite arrays—e.g., at ribosomal DNA and centromeres—displayed high ssDNA levels, implicating non-B DNA in satellite expansion and function. Hidden Markov Models applied to our ssDNA data revealed active genomic domains with specific functions—e.g., replication, transcription, or recombination—each enriched in particular non-B DNA types. Human-specific ssDNA domains correlated with nervous system genes, whereas cancer and embryonic cells showed increased ssDNA in transposable elements. Our ssDNA analysis across ape T2T genomes uncovered conserved and species-specific DNA structural dynamics central to genome regulation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559445,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"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":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":823719,"name":"Huiqing Zeng","orcid":null,"position":1,"is_corresponding":false},{"id":842665,"name":"Hana Pálová","orcid":"0000-0001-8803-9433","position":2,"is_corresponding":false},{"id":21323,"name":"Linnéa Smeds","orcid":"0000-0002-8415-9259","position":3,"is_corresponding":false},{"id":24513,"name":"Saswat K. Mohanty","orcid":"0000-0002-1813-589X","position":4,"is_corresponding":false},{"id":1274725,"name":"Angelika Lahnsteiner","orcid":"0000-0001-7402-3369","position":5,"is_corresponding":false},{"id":19593,"name":"Francesca Chiaromonte","orcid":"0000-0001-5605-9886","position":6,"is_corresponding":false},{"id":19591,"name":"Kateryna D. Makova","orcid":"0000-0002-6212-9526","position":7,"is_corresponding":false},{"id":913567,"name":"Jacob P. Sieg","orcid":"0000-0001-5414-1667","position":0,"is_corresponding":true}],"reference_count":146,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41279030","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":[]}