{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:21:37Z","timestamp":1769041297361,"version":"3.49.0"},"reference-count":87,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T00:00:00Z","timestamp":1656115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG000741"],"award-info":[{"award-number":["AG000741"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary breast and ovarian cancers are frequently attributed to germline mutations in the tumor suppressor genes <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic>. BRCA1\/2 act to repair double\u2010strand breaks (DSBs) and suppress the demise of unstable replication forks. Our work elucidated a dynamic interplay between BRCA2 and the WRN DNA helicase\/exonuclease defective in the premature aging disorder Werner syndrome. WRN and BRCA2 participate in complementary pathways to stabilize replication forks in cancer cells, allowing them to proliferate. Whether the functional overlap of WRN and BRCA2 is relevant to replication at gaps between newly synthesized DNA fragments, protection of telomeres, and\/or metabolism of secondary DNA structures remain to be determined. Advances in understanding the mechanisms elicited during replication stress have prompted the community to reconsider avenues for cancer therapy. Insights from studies of PARP or topoisomerase inhibitors provide working models for the investigation of WRN's mechanism of action. We discuss these topics, focusing on the implications of the <jats:italic>WRN\u2010BRCA2<\/jats:italic> genetic interaction under conditions of replication stress.<\/jats:p>","DOI":"10.1002\/bies.202200057","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T08:00:52Z","timestamp":1656144052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer"],"prefix":"10.1002","volume":"44","author":[{"given":"Arindam","family":"Datta","sequence":"first","affiliation":[{"name":"Helicases and Genomic Integrity Section, Translational Gerontology Branch National Institute on Aging, NIH  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Robert M.","family":"Brosh","sequence":"additional","affiliation":[{"name":"Helicases and Genomic Integrity Section, Translational Gerontology Branch National Institute on Aging, NIH  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,25]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3560"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2020.102994"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201026811\u2010w"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5259.258"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.021"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv836"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201406100"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2021.103209"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100261\u20105"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.06.011"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201020\u20101602"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201026227\u20106"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.08.016"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.09.013"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1389"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.24.19.8437\u20108446.2004"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1321305"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103619"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006338107"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.05.023"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst20170044"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.20.5791"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03\u201008\u20100567"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh234"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki1002"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.02.071"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.18.12797"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.13.2843"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1943"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.278994"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2021.12.005"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010021\u201003921\u20108"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201410061"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006423108"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.12.004"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03443"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03445"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2018.08.021"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2019.07.008"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010018\u20100055\u20106"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29041"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102013\u201005\u2010501072"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010959107"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003910"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.12.6887"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201019\u20101089"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf9246"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010021\u201000807\u20106"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.20.13667"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2012.12.004"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.351338"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102009\u201011\u2010256016"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23128"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI147301"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.024"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.053"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.11.024"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2020.102822"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.08.003"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.053"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab777"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2020.102837"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2020.102926"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba6290"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110034"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201025252\u20109"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107413"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201012\u20102975"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210525"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2016.04.007"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2018.00059"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200803173"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.26320"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101103\u20109"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101102\u2010x"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2019.02.006"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43333"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201020\u20101508"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102769\u20108"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u2010nb2019\u2010055"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.09.001"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586\u2010019\u201001086\u2010w"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1905048"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2021.06.014"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010020\u201002833\u2010z"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.205"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212254"}],"container-title":["BioEssays"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bies.202200057","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bies.202200057","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bies.202200057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:48:23Z","timestamp":1692866903000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bies.202200057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,25]]},"references-count":87,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/bies.202200057"],"URL":"https:\/\/doi.org\/10.1002\/bies.202200057","archive":["Portico"],"relation":{},"ISSN":["0265-9247","1521-1878"],"issn-type":[{"value":"0265-9247","type":"print"},{"value":"1521-1878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,25]]},"assertion":[{"value":"2022-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2200057"}}