{"doi":"10.1038/s41594-024-01279-6","title":"Deregulated DNA ADP-ribosylation impairs telomere replication","abstract":"The recognition that DNA can be ADP ribosylated provides an unexpected regulatory level of how ADP-ribosylation contributes to genome stability, epigenetics and immunity. Yet, it remains unknown whether DNA ADP-ribosylation (DNA-ADPr) promotes genome stability and how it is regulated. Here, we show that telomeres are subject to DNA-ADPr catalyzed by PARP1 and removed by TARG1. Mechanistically, we show that DNA-ADPr is coupled to lagging telomere DNA strand synthesis, forming at single-stranded DNA present at unligated Okazaki fragments and on the 3' single-stranded telomere overhang. Persistent DNA-linked ADPr, due to TARG1 deficiency, eventually leads to telomere shortening. Furthermore, using the bacterial DNA ADP-ribosyl-transferase toxin to modify DNA at telomeres directly, we demonstrate that unhydrolyzed DNA-linked ADP-ribose compromises telomere replication and telomere integrity. Thus, by identifying telomeres as chromosomal targets of PARP1 and TARG1-regulated DNA-ADPr, whose deregulation compromises telomere replication and integrity, our study highlights and establishes the critical importance of controlling DNA-ADPr turnover for sustained genome stability.","journal":"Nature Structural & Molecular Biology","year":2024,"id":423307,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1189789,"name":"Junyeop Lee","orcid":"0000-0002-6367-9183","position":1,"is_corresponding":false},{"id":1218401,"name":"Robert Lu","orcid":"0000-0001-7483-9691","position":2,"is_corresponding":false},{"id":289468,"name":"M. Schuller","orcid":"0000-0002-1551-0359","position":3,"is_corresponding":false},{"id":635069,"name":"Joséphine Groslambert","orcid":"0000-0002-3254-2854","position":4,"is_corresponding":false},{"id":327756,"name":"Ragini Bhargava","orcid":null,"position":5,"is_corresponding":false},{"id":894709,"name":"Sandra Schamus-Haynes","orcid":null,"position":6,"is_corresponding":false},{"id":1219041,"name":"Leyneir C. Cespedes","orcid":null,"position":7,"is_corresponding":false},{"id":323491,"name":"Patricia L. Opresko","orcid":"0000-0002-6470-2189","position":8,"is_corresponding":false},{"id":13921,"name":"Hilda A. Pickett","orcid":"0000-0002-9840-4841","position":9,"is_corresponding":false},{"id":1008329,"name":"Jaewon Min","orcid":"0000-0002-2065-0428","position":10,"is_corresponding":false},{"id":263641,"name":"Ivan Ahel","orcid":"0000-0002-9446-3756","position":11,"is_corresponding":false},{"id":326575,"name":"Roderick J. O’Sullivan","orcid":"0000-0002-0289-0911","position":12,"is_corresponding":false},{"id":327758,"name":"Anne R. Wondisford","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:57:56.814994Z","pmid":"38714889","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":[]}