{"id":"https://openalex.org/W7215910474","doi":"https://doi.org/10.64898/2026.10.01.756001","title":"Direct CDK1 engagement underlies carbaryl-induced genotoxic cell cycle arrest","display_name":"Direct CDK1 engagement underlies carbaryl-induced genotoxic cell cycle arrest","publication_year":2026,"publication_date":"2026-10-02","ids":{"openalex":"https://openalex.org/W7215910474","doi":"https://doi.org/10.64898/2026.10.01.756001"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.01.756001","doi":"https://doi.org/10.64898/2026.10.01.756001","is_oa":false,"landing_page_url":"https://doi.org/10.64898/2026.10.01.756001","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":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5047933825","display_name":"Ravikant Piyush","orcid":"https://orcid.org/0000-0001-8460-9072","observed_orcids":["https://orcid.org/0000-0001-8460-9072"]},"institutions":[{"id":"https://openalex.org/I162827531","display_name":"Indian Institute of Technology Bombay","ror":"https://ror.org/02qyf5152","country_code":"IN","type":"education","lineage":["https://openalex.org/I162827531"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Ravikant Piyush","raw_affiliation_strings":["Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India","institution_ids":["https://openalex.org/I162827531"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5093698034","display_name":"Sumedh Tayade","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I162827531","display_name":"Indian Institute of Technology Bombay","ror":"https://ror.org/02qyf5152","country_code":"IN","type":"education","lineage":["https://openalex.org/I162827531"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Sumedh Tayade","raw_affiliation_strings":["Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India","institution_ids":["https://openalex.org/I162827531"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5066279027","display_name":"Swapnil Rohidas Shinde","orcid":"https://orcid.org/0000-0001-7277-5647","observed_orcids":["https://orcid.org/0000-0001-7277-5647"]},"institutions":[{"id":"https://openalex.org/I162827531","display_name":"Indian Institute of Technology Bombay","ror":"https://ror.org/02qyf5152","country_code":"IN","type":"education","lineage":["https://openalex.org/I162827531"]}],"countries":["IN"],"is_corresponding":true,"raw_author_name":"Swapnil Rohidas Shinde","raw_affiliation_strings":["Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India","institution_ids":["https://openalex.org/I162827531"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5066279027"],"corresponding_institution_ids":["https://openalex.org/I162827531"],"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/T10433","display_name":"Carcinogens and Genotoxicity Assessment","score":0.9154999852180481,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T10433","display_name":"Carcinogens and Genotoxicity Assessment","score":0.9154999852180481,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T10583","display_name":"Cancer-related Molecular Pathways","score":0.029999999329447746,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10875","display_name":"Pesticide Exposure and Toxicity","score":0.020899999886751175,"subfield":{"id":"https://openalex.org/subfields/1110","display_name":"Plant Science"},"field":{"id":"https://openalex.org/fields/11","display_name":"Agricultural and Biological Sciences"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/carbaryl","display_name":"carbaryl","score":1.0},{"id":"https://openalex.org/keywords/carbamate-pesticides","display_name":"carbamate pesticides","score":0.8999999761581421},{"id":"https://openalex.org/keywords/cdk1","display_name":"CDK1","score":0.7929999828338623},{"id":"https://openalex.org/keywords/cdk2","display_name":"CDK2","score":0.8320000171661377},{"id":"https://openalex.org/keywords/genotoxicity","display_name":"genotoxicity","score":0.8069999814033508},{"id":"https://openalex.org/keywords/cell-cycle-arrest","display_name":"cell cycle arrest","score":0.9909999966621399},{"id":"https://openalex.org/keywords/s-phase-arrest","display_name":"S phase arrest","score":0.7910000085830688},{"id":"https://openalex.org/keywords/g2-m-cell-cycle-arrest","display_name":"G2/M cell cycle arrest","score":0.996999979019165},{"id":"https://openalex.org/keywords/dna-damage","display_name":"DNA damage","score":0.6470000147819519},{"id":"https://openalex.org/keywords/mitotic-arrest","display_name":"mitotic arrest","score":0.8040000200271606},{"id":"https://openalex.org/keywords/renal-tubular-epithelial-cells","display_name":"renal tubular epithelial cells","score":0.8140000104904175},{"id":"https://openalex.org/keywords/chronic-kidney-disease-of-unknown-etiology","display_name":"chronic kidney disease of unknown etiology","score":0.8960000276565552},{"id":"https://openalex.org/keywords/molecular-dynamics-simulation","display_name":"molecular dynamics simulation","score":0.5120000243186951},{"id":"https://openalex.org/keywords/cellular-thermal-shift-assay","display_name":"cellular thermal shift assay","score":0.8190000057220459}],"concepts":[{"id":"https://openalex.org/C120504264","wikidata":"https://www.wikidata.org/wiki/Q1147372","display_name":"Cyclin-dependent kinase 1","level":4,"score":0.5598999857902527},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5169000029563904},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.5148000121116638},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5090000033378601},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.4643000066280365},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.44839999079704285},{"id":"https://openalex.org/C2780358455","wikidata":"https://www.wikidata.org/wiki/Q903780","display_name":"Comet assay","level":4,"score":0.43799999356269836},{"id":"https://openalex.org/C105696609","wikidata":"https://www.wikidata.org/wiki/Q1068809","display_name":"Cell cycle checkpoint","level":4,"score":0.42419999837875366},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.4219000041484833},{"id":"https://openalex.org/C114246631","wikidata":"https://www.wikidata.org/wiki/Q187661","display_name":"Carcinogen","level":2,"score":0.4131999909877777},{"id":"https://openalex.org/C93304396","wikidata":"https://www.wikidata.org/wiki/Q14763008","display_name":"Mitosis","level":2,"score":0.3799000084400177},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.37459999322891235},{"id":"https://openalex.org/C2780091579","wikidata":"https://www.wikidata.org/wiki/Q9377","display_name":"Kidney","level":2,"score":0.3725000023841858},{"id":"https://openalex.org/C2776051353","wikidata":"https://www.wikidata.org/wiki/Q415090","display_name":"Carbaryl","level":3,"score":0.36000001430511475},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3465999960899353},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.34610000252723694},{"id":"https://openalex.org/C64927066","wikidata":"https://www.wikidata.org/wiki/Q36293","display_name":"Histone","level":3,"score":0.33379998803138733},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.3102000057697296},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.29030001163482666},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.28769999742507935},{"id":"https://openalex.org/C2780381497","wikidata":"https://www.wikidata.org/wiki/Q463418","display_name":"Fibroblast","level":3,"score":0.27320000529289246},{"id":"https://openalex.org/C124320809","wikidata":"https://www.wikidata.org/wiki/Q46292","display_name":"Cyclin-dependent kinase","level":4,"score":0.27140000462532043}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.01.756001","doi":"https://doi.org/10.64898/2026.10.01.756001","is_oa":false,"landing_page_url":"https://doi.org/10.64898/2026.10.01.756001","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":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9476000070571899}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":31,"referenced_works":["https://openalex.org/W1120049889","https://openalex.org/W1977783506","https://openalex.org/W2010088746","https://openalex.org/W2014936015","https://openalex.org/W2026143081","https://openalex.org/W2029606078","https://openalex.org/W2048069174","https://openalex.org/W2048310326","https://openalex.org/W2054767020","https://openalex.org/W2057020479","https://openalex.org/W2058891255","https://openalex.org/W2076849434","https://openalex.org/W2088120691","https://openalex.org/W2091772125","https://openalex.org/W2113604152","https://openalex.org/W2132066963","https://openalex.org/W2138108066","https://openalex.org/W2164660906","https://openalex.org/W2168194813","https://openalex.org/W2413588373","https://openalex.org/W2497884895","https://openalex.org/W2591210164","https://openalex.org/W2990659946","https://openalex.org/W3087573264","https://openalex.org/W3092073378","https://openalex.org/W3092716975","https://openalex.org/W3122175558","https://openalex.org/W3138667811","https://openalex.org/W3216238012","https://openalex.org/W4213424637","https://openalex.org/W4411848196"],"related_works":["https://openalex.org/W2754437846","https://openalex.org/W2039966444","https://openalex.org/W2020120430","https://openalex.org/W2091772125","https://openalex.org/W2024890393","https://openalex.org/W2573863316","https://openalex.org/W4233657735","https://openalex.org/W183179820","https://openalex.org/W1840477957","https://openalex.org/W3138667811"],"abstract_inverted_index":{"Abstract":[0],"Carbaryl,":[1],"a":[2,59,83,91,94,100,153,185,203,216],"widely":[3],"used":[4],"carbamate":[5],"pesticide,":[6],"has":[7],"been":[8],"epidemiologically":[9],"associated":[10],"with":[11,178,207,225],"genotoxic":[12],"and":[13,48,67,77,112,120,134,146,164,193,214,227],"carcinogenic":[14],"outcomes":[15],"in":[16,29,82,231],"exposed":[17,232],"human":[18,233],"populations,":[19],"including":[20],"elevated":[21],"cancer":[22],"risk":[23],"at":[24],"several":[25],"tissue":[26,229],"sites":[27],"and,":[28,89],"some":[30],"agricultural":[31],"communities,":[32],"chronic":[33],"tubulointerstitial":[34],"kidney":[35],"disease":[36],"of":[37,61,64,130,156],"unknown":[38],"etiology":[39],"(CKDu).":[40],"However,":[41],"the":[42,160,190],"cellular":[43,142],"mechanisms":[44],"underlying":[45],"these":[46,198],"associations,":[47],"whether":[49],"carbaryl":[50,72,109,158,201],"acts":[51],"uniformly":[52],"across":[53],"tissues,":[54],"remain":[55],"poorly":[56],"defined.":[57],"Screening":[58],"panel":[60],"cell":[62,78],"lines":[63],"distinct":[65],"species":[66],"lineage,":[68],"we":[69],"found":[70],"that":[71],"elicits":[73],"pronounced,":[74],"dose-dependent":[75],"cytotoxicity":[76],"cycle":[79],"arrest":[80,114,195],"selectively":[81],"renal":[84,226],"tubular":[85],"epithelial":[86,96],"line":[87,97,102],"(IMCD3)":[88],"to":[90,118],"lesser":[92],"extent,":[93],"cervical":[95],"(HeLa),":[98],"while":[99],"fibroblast":[101],"(NIH3T3)":[103],"was":[104],"unaffected.":[105],"In":[106],"IMCD3":[107],"cells,":[108],"induces":[110],"S-":[111],"G2/M-phase":[113],"through":[115,173],"direct":[116,154],"binding":[117],"DNA":[119,122],"consequent":[121],"damage,":[123],"triggers":[124],"Bcl-2":[125],"-mediated":[126],"late":[127],"apoptosis":[128],"independently":[129],"reactive":[131],"oxygen":[132],"species,":[133],"drives":[135],"irreversible":[136],"mitotic":[137],"arrest.":[138],"Molecular":[139],"dynamics":[140],"simulations,":[141],"thermal":[143],"shift":[144],"assays,":[145],"kinase":[147],"measurements":[148],"converge":[149],"on":[150,212],"CDK1":[151,161],"as":[152,202],"target":[155],"carbaryl:":[157],"destabilises":[159],"active":[162],"site":[163],"inhibits":[165],"its":[166,222],"catalytic":[167],"activity,":[168],"whereas":[169],"CDK2":[170],"is":[171],"engaged":[172],"an":[174],"opposing,":[175],"rigidifying":[176],"mode":[177],"no":[179],"functional":[180],"consequence.":[181],"This":[182],"asymmetry":[183],"provides":[184],"coherent":[186],"mechanistic":[187,218],"basis":[188],"for":[189,220],"combined":[191],"S-phase":[192],"G2/M":[194],"observed.":[196],"Together,":[197],"findings":[199],"establish":[200],"genotoxic,":[204],"cell-cycle-disrupting":[205],"agent":[206],"tissue-selective":[208],"potency":[209],"acting":[210],"directly":[211],"CDK1,":[213],"provide":[215],"cell-based":[217],"framework":[219],"interpreting":[221],"reported":[223],"associations":[224],"other":[228],"pathologies":[230],"populations.":[234]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-10-03T00:00:00"}