{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:29:58Z","timestamp":1790897398905,"version":"4.1.0"},"reference-count":107,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM134537"],"award-info":[{"award-number":["GM134537"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of California Office of the president Cancer Research Coordinating Committee (UCOP CRCC) Pilot Grant","award":["C23CR5562"],"award-info":[{"award-number":["C23CR5562"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,8,26]]},"abstract":"<jats:p>DNA secondary G-quadruplex (G4) structures can impair and even obstruct DNA replication. Defects in processing G4 structures are associated with replication stress, a common property of both B cell cancers and hyperproliferative premalignant cells. Genome instability arising from replication stress is a hallmark of cancer and strongly contributes to the chromosome rearrangements in B cell cancers. Here, we define the impact of G4-stabilizing ligands on generating genome instability in primary and malignant B cells. Treatment with the G4-stabilizing compound pyridostatin (PDS) causes breaks and chromosome rearrangements at ribosomal DNA and pericentromeric major satellite regions in both mouse primary B cell culture and CH12 lymphoma cells. PDS also causes extensive pericentromeric DNA damage in immortalized human B cell lines. Remarkably, PDS causes high level of tetraploid metaphase cells correlated with high level of dicentric chromosomes specifically in primary but not in CH12 B cells. Unlike primary B cells, CH12 cells undergo checkpoint activation and strong G2\/M arrest in response to PDS treatment thus preventing tetraploid appearance. Altogether, these results highlight the difference between primary and malignant B cells in response to PDS, revealing the therapeutic potential of G4-stabilizing drugs to selectively suppress tumor cell growth and proliferation.<\/jats:p>","DOI":"10.1073\/pnas.2506939122","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T14:49:18Z","timestamp":1755701358000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["G-quadruplex stabilization induces DNA breaks in pericentromeric repetitive DNA sequences in B lymphocytes"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8107-6263","authenticated-orcid":false,"given":"Irina","family":"Waisertreiger","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California Davis","place":["Davis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalkidan","family":"Ayele","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California Davis","place":["Davis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehad Hilal","family":"Elshaikh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California Davis","place":["Davis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9042-6245","authenticated-orcid":false,"given":"Jacqueline H.","family":"Barlow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California Davis","place":["Davis"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv862"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki609"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki553"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3662"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.150"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa841"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3295"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01781"},{"key":"e_1_3_4_9_2","first-page":"10230","article-title":"Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq)","volume":"44","author":"Langley A. R.","year":"2016","unstructured":"A. R. Langley, S. Graf, J. C. Smith, T. Krude, Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq). Nucleic Acids Res. 44, 10230\u201310247 (2016).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11104-0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012930"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl286"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.121830.111"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2339"},{"key":"e_1_3_4_15_2","first-page":"163","volume-title":"Annual Reports in Medicinal Chemistry","author":"Pirota V.","year":"2020","unstructured":"V. Pirota, M. Stasi, A. Benassi, F. Doria, \u201cChapter Six\u2013An overview of quadruplex ligands: Their common features and chemotype diversity\u201d in Annual Reports in Medicinal Chemistry, S. Neidle, Ed. (Academic Press, 2020), pp. 163\u2013196."},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.842"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trechm.2019.07.002"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c04775"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.780"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja404868t"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114501"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.12.004"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14432"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2011.04.013"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.316"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12149"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt804"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.783889"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31657-x"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17176-7"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810409116"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101282"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/8743"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.6.1317"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102770"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.2.193"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm986"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.22.15908"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2020.593692"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.03.010"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2006.01.014"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22129-9"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1292"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/dsz008"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl253"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz087"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10802"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01866"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1678"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1829209"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.080531"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04217"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.04.043"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2007.02.011"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000386"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3317838"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21050663"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1385\/MB:32:3:227"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7480"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2020.3"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-1054-5"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes13071144"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00298"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.03.036"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00281"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC05816A"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00272988"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.01.006"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.1c08340"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65184"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00568"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy010"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt957"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.22.12159"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4178"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2773"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.006"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112062"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2201"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201011083"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04200-z"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.01.004"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0672-8"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj5089"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abk3112"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.145"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813926"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.88"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008821"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601127"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080044"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904085"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08605.x"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-023-00682-x"},{"key":"e_1_3_4_95_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl529"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv063"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13485"},{"key":"e_1_3_4_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.03.178"},{"key":"e_1_3_4_99_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-718171"},{"key":"e_1_3_4_100_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1455"},{"key":"e_1_3_4_101_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46793"},{"key":"e_1_3_4_102_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(200006)191:2<181::AID-PATH607>3.0.CO;2-V"},{"key":"e_1_3_4_103_2","doi-asserted-by":"publisher","DOI":"10.1159\/000108316"},{"key":"e_1_3_4_104_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31885"},{"key":"e_1_3_4_105_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006423108"},{"key":"e_1_3_4_106_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(03)00199-X"},{"key":"e_1_3_4_107_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90176-0"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2506939122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T14:49:35Z","timestamp":1755701375000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2506939122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":107,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2025,8,26]]}},"alternative-id":["10.1073\/pnas.2506939122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2506939122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]},"assertion":[{"value":"2025-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2506939122"}}