{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Melikishvili M"],"funding":["NIEHS NIH HHS"],"pagination":["7530"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10980755"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["Poly (ADP)-ribose polymerase 1 (PARP1) is an abundant nuclear protein well-known for its role in DNA repair yet also participates in DNA replication, transcription, and co-transcriptional splicing, where DNA is undamaged. Thus, binding to undamaged regions in DNA and RNA is likely a part of PARP1's normal repertoire. Here we describe analyses of PARP1 binding to two short single-stranded DNAs, a single-stranded RNA, and a double stranded DNA. The investigations involved comparing the wild-type (WT) full-length enzyme with mutants lacking the catalytic domain (∆CAT) or zinc fingers 1 and 2 (∆Zn1∆Zn2). All three protein types exhibited monomeric characteristics in solution and formed saturated 2:1 complexes with single-stranded T<sub>20</sub> and U<sub>20</sub> oligonucleotides. These complexes formed without accumulation of 1:1 intermediates, a pattern suggestive of positive binding cooperativity. The retention of binding activities by ∆CAT and ∆Zn1∆Zn2 enzymes suggests that neither the catalytic domain nor zinc fingers 1 and 2 are indispensable for cooperative binding. In contrast, when a double stranded 19mer DNA was tested, WT PARP1 formed a 4:1 complex while the ∆Zn1Zn2 mutant binding saturated at 1:1 stoichiometry. These deviations from the 2:1 pattern observed with T<sub>20</sub> and U<sub>20</sub> oligonucleotides show that PARP's binding mechanism can be influenced by the secondary structure of the nucleic acid. Our studies show that PARP1:nucleic acid interactions are strongly dependent on the nucleic acid type and properties, perhaps reflecting PARP1's ability to respond differently to different nucleic acid ligands in cells. These findings lay a platform for understanding how the functionally versatile PARP1 recognizes diverse oligonucleotides within the realms of chromatin and RNA biology."],"journal":["Scientific reports"],"pubmed_title":["Cooperative nucleic acid binding by Poly ADP-ribose polymerase 1."],"pmcid":["PMC10980755"],"funding_grant_id":["R01ES034253"],"pubmed_authors":["Fondufe-Mittendorf YN","Melikishvili M","Fried MG"],"additional_accession":[]},"is_claimable":false,"name":"Cooperative nucleic acid binding by Poly ADP-ribose polymerase 1.","description":"Poly (ADP)-ribose polymerase 1 (PARP1) is an abundant nuclear protein well-known for its role in DNA repair yet also participates in DNA replication, transcription, and co-transcriptional splicing, where DNA is undamaged. Thus, binding to undamaged regions in DNA and RNA is likely a part of PARP1's normal repertoire. Here we describe analyses of PARP1 binding to two short single-stranded DNAs, a single-stranded RNA, and a double stranded DNA. The investigations involved comparing the wild-type (WT) full-length enzyme with mutants lacking the catalytic domain (∆CAT) or zinc fingers 1 and 2 (∆Zn1∆Zn2). All three protein types exhibited monomeric characteristics in solution and formed saturated 2:1 complexes with single-stranded T<sub>20</sub> and U<sub>20</sub> oligonucleotides. These complexes formed without accumulation of 1:1 intermediates, a pattern suggestive of positive binding cooperativity. The retention of binding activities by ∆CAT and ∆Zn1∆Zn2 enzymes suggests that neither the catalytic domain nor zinc fingers 1 and 2 are indispensable for cooperative binding. In contrast, when a double stranded 19mer DNA was tested, WT PARP1 formed a 4:1 complex while the ∆Zn1Zn2 mutant binding saturated at 1:1 stoichiometry. These deviations from the 2:1 pattern observed with T<sub>20</sub> and U<sub>20</sub> oligonucleotides show that PARP's binding mechanism can be influenced by the secondary structure of the nucleic acid. Our studies show that PARP1:nucleic acid interactions are strongly dependent on the nucleic acid type and properties, perhaps reflecting PARP1's ability to respond differently to different nucleic acid ligands in cells. These findings lay a platform for understanding how the functionally versatile PARP1 recognizes diverse oligonucleotides within the realms of chromatin and RNA biology.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-04T20:16:25.395Z","creation":"2025-04-04T20:16:25.395Z"},"accession":"S-EPMC10980755","cross_references":{"pubmed":["38553566"],"doi":["10.1038/s41598-024-58076-w"]}}