{"doi":"10.1126/science.aax6367","title":"Structural basis for allosteric PARP-1 retention on DNA breaks","abstract":"The success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. Although different forms of PARPi all target the catalytic center of the enzyme, they have variable abilities to trap PARP-1. We found that several structurally distinct PARPi drive PARP-1 allostery to promote release from a DNA break. Other inhibitors drive allostery to retain PARP-1 on a DNA break. Further, we generated a new PARPi compound, converting an allosteric pro-release compound to a pro-retention compound and increasing its ability to kill cancer cells. These developments are pertinent to clinical applications where PARP-1 trapping is either desirable or undesirable.","journal":"Science","year":2020,"id":48831,"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":336,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232702,"name":"Marie-France Langelier","orcid":"0000-0001-9815-1840","position":1,"is_corresponding":false},{"id":232703,"name":"Uday Kiran Velagapudi","orcid":"0000-0002-3850-5624","position":2,"is_corresponding":false},{"id":232704,"name":"Mark A. Hancock","orcid":"0000-0001-7427-7449","position":3,"is_corresponding":false},{"id":232705,"name":"Jamin D. Steffen","orcid":"0000-0001-7589-1811","position":4,"is_corresponding":false},{"id":232706,"name":"Ramya Billur","orcid":"0000-0002-8677-0801","position":5,"is_corresponding":false},{"id":232707,"name":"Zain M. Hannan","orcid":"0000-0002-3714-9779","position":6,"is_corresponding":false},{"id":232708,"name":"Andrew J. Wicks","orcid":"0000-0002-9307-3262","position":7,"is_corresponding":false},{"id":232709,"name":"Dragomir B. Krastev","orcid":"0000-0003-4298-7272","position":8,"is_corresponding":false},{"id":232710,"name":"Stephen J. Pettitt","orcid":"0000-0003-3313-3857","position":9,"is_corresponding":false},{"id":75497,"name":"Christopher J. Lord","orcid":"0000-0002-3226-0515","position":10,"is_corresponding":false},{"id":232711,"name":"Tanaji T. Talele","orcid":"0000-0002-5938-6505","position":11,"is_corresponding":false},{"id":232712,"name":"John M. Pascal","orcid":"0000-0002-2714-4317","position":12,"is_corresponding":false},{"id":232713,"name":"Ben E. Black","orcid":"0000-0002-3707-9483","position":13,"is_corresponding":false},{"id":234477,"name":"Levani Zandarashvili","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T20:35:18.908826Z","pmid":"32241924","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":[]}