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We wanted to understand why BKPyV-induced activation of the DNA damage response (DDR) enhances viral titers and prevents host DNA damage. Here, we show that the virus activates the DNA damage response in order to keep the infected cells in S phase to replicate the viral DNA. The source of DNA damage was due to actively replicating cells with uncondensed chromosomes entering directly into mitosis when the DDR was inhibited in BKPyV-infected cells. This study clarifies the previously enigmatic role of the DDR during BKPyV infection by demonstrating that the virus activates the DDR to maintain the cells in S phase in order to promote viral replication and that disruption of this cell cycle arrest can lead to catastrophic DNA damage for the host.<\/jats:p>","DOI":"10.1128\/jvi.00130-19","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T10:54:41Z","timestamp":1556276081000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["BK Polyomavirus Activates the DNA Damage Response To Prolong S Phase"],"prefix":"10.1128","volume":"93","author":[{"given":"Joshua L.","family":"Justice","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Needham","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7338-8822","authenticated-orcid":false,"given":"Sunnie R.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2012.02.002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.5127"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092611-150154"},{"key":"e_1_3_2_5_2","first-page":"101","article-title":"Cellular localization and T antigen binding of the retinoblastoma protein","volume":"7","author":"Bartek J","year":"1992","unstructured":"Bartek J, Vojtesek B, Grand RJ, Gallimore PH, Lane DP. 1992. 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