{"id":"https://openalex.org/W7207517890","doi":"https://doi.org/10.64898/2026.09.01.748521","title":"Trans-branching of polyubiquitin chains orchestrates the DNA replication stress response","display_name":"Trans-branching of polyubiquitin chains orchestrates the DNA replication stress response","publication_year":2026,"publication_date":"2026-09-03","ids":{"openalex":"https://openalex.org/W7207517890","doi":"https://doi.org/10.64898/2026.09.01.748521"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.01.748521","doi":"https://doi.org/10.64898/2026.09.01.748521","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.01.748521","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.64898/2026.09.01.748521","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5041923544","display_name":"Kirill S. Petriukov","orcid":"https://orcid.org/0000-0001-5386-314X","observed_orcids":["https://orcid.org/0000-0001-5386-314X"]},"institutions":[{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Kirill Petriukov","raw_affiliation_strings":["Danish Cancer Institute, DK-2100 Copenhagen \u00d8","Institute of Molecular Biology; 55128 Mainz, Germany"],"raw_orcid":"https://orcid.org/0000-0001-5386-314X","affiliations":[{"raw_affiliation_string":"Danish Cancer Institute, DK-2100 Copenhagen \u00d8","institution_ids":[]},{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039926703","display_name":"Christian Renz","orcid":"https://orcid.org/0000-0003-3164-3597","observed_orcids":["https://orcid.org/0000-0003-3164-3597"]},"institutions":[{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Christian Renz","raw_affiliation_strings":["Institute of Molecular Biology; 55128 Mainz, Germany"],"raw_orcid":"https://orcid.org/0000-0003-3164-3597","affiliations":[{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5149558597","display_name":"Markus S Schraft","orcid":"https://orcid.org/0009-0007-8092-9651","observed_orcids":["https://orcid.org/0009-0007-8092-9651"]},"institutions":[{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Markus S. Schraft","raw_affiliation_strings":["Institute of Molecular Biology; 55128 Mainz, Germany"],"raw_orcid":"https://orcid.org/0009-0007-8092-9651","affiliations":[{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057961219","display_name":"Ivan Miki\u010di\u0107","orcid":"https://orcid.org/0000-0003-3393-0688","observed_orcids":["https://orcid.org/0000-0003-3393-0688"]},"institutions":[{"id":"https://openalex.org/I124055696","display_name":"University of Copenhagen","ror":"https://ror.org/035b05819","country_code":"DK","type":"education","lineage":["https://openalex.org/I124055696"]},{"id":"https://openalex.org/I2801134892","display_name":"Novo Nordisk Foundation","ror":"https://ror.org/04txyc737","country_code":"DK","type":"facility","lineage":["https://openalex.org/I2801134892"]},{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE","DK"],"is_corresponding":false,"raw_author_name":"Ivan Mikicic","raw_affiliation_strings":["Institute of Molecular Biology; 55128 Mainz, Germany","Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen N"],"raw_orcid":"https://orcid.org/0000-0003-3393-0688","affiliations":[{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]},{"raw_affiliation_string":"Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen N","institution_ids":["https://openalex.org/I124055696","https://openalex.org/I2801134892"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5051269714","display_name":"Nils Krapoth","orcid":"https://orcid.org/0000-0001-6809-9906","observed_orcids":["https://orcid.org/0000-0001-6809-9906"]},"institutions":[{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Nils C. Krapoth","raw_affiliation_strings":["Institute of Molecular Biology; 55128 Mainz, Germany"],"raw_orcid":"https://orcid.org/0000-0001-6809-9906","affiliations":[{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5149611566","display_name":"Abhik Thapa","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Abhik Thapa","raw_affiliation_strings":["Institute of Molecular Biology; 55128 Mainz, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012146784","display_name":"Petra Beli","orcid":"https://orcid.org/0000-0001-9507-9820","observed_orcids":["https://orcid.org/0000-0001-9507-9820"]},"institutions":[{"id":"https://openalex.org/I197323543","display_name":"Johannes Gutenberg University Mainz","ror":"https://ror.org/023b0x485","country_code":"DE","type":"education","lineage":["https://openalex.org/I197323543"]},{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Petra Beli","raw_affiliation_strings":["Institute for Developmental Biology and Neurobiology, Johannes Gutenberg-Universit\u00e4t; 55128 Mainz, Germany","Institute of Molecular Biology; 55128 Mainz, Germany"],"raw_orcid":"https://orcid.org/0000-0001-9507-9820","affiliations":[{"raw_affiliation_string":"Institute for Developmental Biology and Neurobiology, Johannes Gutenberg-Universit\u00e4t; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I197323543"]},{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5077688118","display_name":"Helle D. Ulrich","orcid":"https://orcid.org/0000-0003-0431-2223","observed_orcids":["https://orcid.org/0000-0003-0431-2223"]},"institutions":[{"id":"https://openalex.org/I4210165538","display_name":"Institute of Molecular Biology","ror":"https://ror.org/05kxtq558","country_code":"DE","type":"facility","lineage":["https://openalex.org/I4210165538"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Helle D. Ulrich","raw_affiliation_strings":["Institute of Molecular Biology; 55128 Mainz, Germany"],"raw_orcid":"https://orcid.org/0000-0003-0431-2223","affiliations":[{"raw_affiliation_string":"Institute of Molecular Biology; 55128 Mainz, Germany","institution_ids":["https://openalex.org/I4210165538"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5077688118"],"corresponding_institution_ids":["https://openalex.org/I4210165538"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.8535000085830688,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.8535000085830688,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10123","display_name":"DNA Repair Mechanisms","score":0.13539999723434448,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10492","display_name":"Microtubule and mitosis dynamics","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/polyubiquitin-chains","display_name":"polyubiquitin chains","score":0.8360000252723694},{"id":"https://openalex.org/keywords/branched-ubiquitin-chains","display_name":"branched ubiquitin chains","score":0.8489999771118164},{"id":"https://openalex.org/keywords/pcna","display_name":"PCNA","score":0.8140000104904175},{"id":"https://openalex.org/keywords/ube2k","display_name":"UBE2K","score":0.9459999799728394},{"id":"https://openalex.org/keywords/replication-stress","display_name":"replication stress","score":0.6240000128746033},{"id":"https://openalex.org/keywords/replication-fork-stalling","display_name":"replication fork stalling","score":0.7110000252723694},{"id":"https://openalex.org/keywords/valosin-containing-protein","display_name":"VCP","score":0.550000011920929},{"id":"https://openalex.org/keywords/brca1","display_name":"BRCA1","score":0.9620000123977661},{"id":"https://openalex.org/keywords/usp1","display_name":"USP1","score":0.8970000147819519},{"id":"https://openalex.org/keywords/chromatin","display_name":"chromatin","score":0.5910000205039978}],"concepts":[{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.7713000178337097},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.6261000037193298},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5511999726295471},{"id":"https://openalex.org/C73573662","wikidata":"https://www.wikidata.org/wiki/Q130996","display_name":"DNA replication","level":3,"score":0.5422000288963318},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.5223000049591064},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.42570000886917114},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.41929998993873596},{"id":"https://openalex.org/C12590798","wikidata":"https://www.wikidata.org/wiki/Q3933199","display_name":"Replication (statistics)","level":2,"score":0.3961000144481659},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.35830000042915344},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.34290000796318054},{"id":"https://openalex.org/C98086919","wikidata":"https://www.wikidata.org/wiki/Q118019","display_name":"Eukaryotic DNA replication","level":4,"score":0.33550000190734863},{"id":"https://openalex.org/C94966510","wikidata":"https://www.wikidata.org/wiki/Q2252764","display_name":"DNA-binding protein","level":4,"score":0.3140999972820282},{"id":"https://openalex.org/C34688535","wikidata":"https://www.wikidata.org/wiki/Q418732","display_name":"Proliferating cell nuclear antigen","level":3,"score":0.310699999332428},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.30799999833106995},{"id":"https://openalex.org/C134935766","wikidata":"https://www.wikidata.org/wiki/Q210538","display_name":"DNA repair","level":3,"score":0.30250000953674316},{"id":"https://openalex.org/C78604142","wikidata":"https://www.wikidata.org/wiki/Q1640582","display_name":"Fight-or-flight response","level":3,"score":0.30000001192092896},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.2964000105857849},{"id":"https://openalex.org/C206175624","wikidata":"https://www.wikidata.org/wiki/Q595731","display_name":"Branching (polymer chemistry)","level":2,"score":0.25839999318122864},{"id":"https://openalex.org/C199216141","wikidata":"https://www.wikidata.org/wiki/Q4995178","display_name":"Conserved sequence","level":4,"score":0.25690001249313354},{"id":"https://openalex.org/C134459356","wikidata":"https://www.wikidata.org/wiki/Q4274835","display_name":"Ubiquitin ligase","level":4,"score":0.25189998745918274}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.01.748521","doi":"https://doi.org/10.64898/2026.09.01.748521","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.01.748521","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.01.748521","doi":"https://doi.org/10.64898/2026.09.01.748521","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.01.748521","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":65,"referenced_works":["https://openalex.org/W1944130357","https://openalex.org/W1966500680","https://openalex.org/W1968943627","https://openalex.org/W1974875206","https://openalex.org/W1986429623","https://openalex.org/W1987211450","https://openalex.org/W1991366673","https://openalex.org/W1993612709","https://openalex.org/W1995740655","https://openalex.org/W2008174897","https://openalex.org/W2026512029","https://openalex.org/W2036321220","https://openalex.org/W2047809194","https://openalex.org/W2056139483","https://openalex.org/W2056870028","https://openalex.org/W2063280340","https://openalex.org/W2079266876","https://openalex.org/W2080752012","https://openalex.org/W2089788910","https://openalex.org/W2092357835","https://openalex.org/W2096057003","https://openalex.org/W2105624689","https://openalex.org/W2119301405","https://openalex.org/W2128579113","https://openalex.org/W2134558237","https://openalex.org/W2140757241","https://openalex.org/W2146512944","https://openalex.org/W2147917253","https://openalex.org/W2169950973","https://openalex.org/W2191666140","https://openalex.org/W2340594125","https://openalex.org/W2530977520","https://openalex.org/W2596330017","https://openalex.org/W2614105666","https://openalex.org/W2615692656","https://openalex.org/W2623921962","https://openalex.org/W2751450140","https://openalex.org/W2756601401","https://openalex.org/W2759812252","https://openalex.org/W2769061006","https://openalex.org/W2906377468","https://openalex.org/W2968833147","https://openalex.org/W2982296996","https://openalex.org/W3014832024","https://openalex.org/W3021944451","https://openalex.org/W3026131189","https://openalex.org/W3128179346","https://openalex.org/W3137197601","https://openalex.org/W3176275742","https://openalex.org/W4205483426","https://openalex.org/W4206527354","https://openalex.org/W4210315051","https://openalex.org/W4220952127","https://openalex.org/W4280490934","https://openalex.org/W4306146226","https://openalex.org/W4363632306","https://openalex.org/W4368356893","https://openalex.org/W4381854928","https://openalex.org/W4389795861","https://openalex.org/W4396721167","https://openalex.org/W4398167156","https://openalex.org/W4399729224","https://openalex.org/W4399996483","https://openalex.org/W4400176877","https://openalex.org/W4400422694"],"related_works":["https://openalex.org/W3004542382","https://openalex.org/W2004782259","https://openalex.org/W2003928652","https://openalex.org/W4409910397","https://openalex.org/W2095245322","https://openalex.org/W3021944451","https://openalex.org/W6907875072","https://openalex.org/W4220952127","https://openalex.org/W1996482638","https://openalex.org/W4406496575"],"abstract_inverted_index":{"Summary":[0],"Polyubiquitin":[1],"chain":[2],"geometry":[3],"dictates":[4],"functional":[5],"consequences":[6],"of":[7,53,58,69,76,84,92,102,104,116],"ubiquitylation":[8],"(":[9,27],"1,":[10],"2":[11],").":[12,29],"Although":[13],"branched":[14],"polyubiquitin":[15],"chains":[16],"are":[17],"abundant":[18],"in":[19,60,109,120],"cells,":[20],"little":[21],"is":[22],"known":[23],"about":[24],"their":[25],"functions":[26],"3\u20135":[28],"Here":[30],"we":[31],"show":[32],"that":[33],"branching":[34,73],"on":[35],"the":[36,43,56,96,100,105],"DNA":[37],"replication":[38,63],"factor":[39],"PCNA,":[40],"mediated":[41],"by":[42],"ubiquitin-conjugating":[44],"enzyme":[45],"UBE2K":[46,117],"and":[47,51,79],"involving":[48],"lysines":[49],"63":[50],"48":[52],"ubiquitin,":[54],"orchestrates":[55],"sequence":[57],"events":[59],"response":[61],"to":[62,118,127],"stress.":[64],"By":[65],"inducing":[66],"VCP-dependent":[67],"extraction":[68],"PCNA":[70],"from":[71],"chromatin,":[72],"promotes":[74],"re-priming":[75],"stalled":[77],"forks":[78],"necessitates":[80],"a":[81,123],"BRCA1-dependent":[82],"pathway":[83],"daughter-strand":[85,93],"gap":[86],"repair.":[87],"Our":[88],"study":[89],"identifies":[90],"hyper-accumulation":[91],"gaps":[94],"as":[95],"mechanistic":[97],"basis":[98],"underlying":[99],"toxicity":[101],"inhibitors":[103],"PCNA-specific":[106],"isopeptidase,":[107],"USP1,":[108],"BRCA1-deficient":[110],"cells.":[111],"Moreover,":[112],"an":[113],"unexpected":[114],"preference":[115],"operate":[119],"trans":[121],"suggests":[122],"general":[124],"timing":[125],"mechanism":[126],"organize":[128],"hierarchies":[129],"amongst":[130],"ubiquitin":[131],"signals.":[132]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2026-09-04T00:00:00"}
