{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:12:42Z","timestamp":1779189162458,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007544","name":"Boler Family Foundation","doi-asserted-by":"publisher","award":["endowment to Xin Lu"],"award-info":[{"award-number":["endowment to Xin Lu"]}],"id":[{"id":"10.13039\/100007544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008109","name":"University of Notre Dame","doi-asserted-by":"publisher","award":["IBMS Graduate Program"],"award-info":[{"award-number":["IBMS Graduate Program"]}],"id":[{"id":"10.13039\/100008109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recent genomic profiling has identified a subtype of prostate cancer (PCa) characterized by two key genetic alterations: missense mutation of speckle\u2010type POZ protein (<jats:italic>SPOP<\/jats:italic>) and homozygous deletion of chromodomain helicase DNA\u2010binding protein 1 (<jats:italic>CHD1<\/jats:italic>). Mutually exclusive with E26 transformation\u2010specific (<jats:italic>ETS<\/jats:italic>) rearrangements, this subtype displays high genomic instability. Previous studies indicate that deficient <jats:italic>SPOP<\/jats:italic> or <jats:italic>CHD1<\/jats:italic> alone leads to feeble prostate abnormalities and each protein is involved in DNA damage response (DDR). It remains to be determined whether CHD1 and SPOP cooperate to suppress prostate tumorigenesis and DDR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Prostate\u2010specific single or double knockout of <jats:italic>Spop<\/jats:italic> and <jats:italic>Chd1<\/jats:italic> was generated with the Cre\/loxP system in mice. Wild\u2010type or mutant <jats:italic>SPOP<\/jats:italic> (F102C, F133V) overexpression and <jats:italic>CHD1<\/jats:italic> knockdown with short hairpin RNA were created in human benign prostatic hyperplasia cell line BPH1. The levels of DNA damage and homologous recombination repair were measured by immunofluorescence staining of \u03b3H2AX and RAD51, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Spop\/Chd1<\/jats:italic> double\u2010knockout mice displayed prostatic intraepithelial neoplasia at both young (3 months) and old (12 months) ages and failed to generate prostate adenocarcinoma. Compared with wild\u2010type or single\u2010knockout mice, the double\u2010knockout prostate harbored moderately higher proliferating cells and dramatically augmented the level of \u03b3H2AX staining, although androgen receptor\u2010positive cells and apoptotic cells remained at a similar level. In BPH1 cell line, <jats:italic>SPOP<\/jats:italic> mutant overexpression and <jats:italic>CHD1<\/jats:italic> silencing synergistically sensitized the cells to DNA damage by camptothecin, an inducer of double\u2010strand breaks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that SPOP and CHD1 can synergistically promote repair of naturally occurring or chemically induced DNA damages in prostate epithelial cells. Regarding the progression of the SPOP\/CHD1 subtype of PCa, other functionally complementary drivers warrant further identification. The clinical implication is that this subtype of PCa may be particularly sensitive to poly(ADP\u2010ribose) polymerase inhibitors or DNA\u2010damaging agents.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24080","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T22:40:21Z","timestamp":1602024021000},"page":"81-88","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CHD1 and SPOP synergistically protect prostate epithelial cells from DNA damage"],"prefix":"10.1002","volume":"81","author":[{"given":"Yini","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Boler\u2010Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute University of Notre Dame  Notre Dame Indiana USA"},{"name":"Integrated Biomedical Sciences Graduate Program University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiling","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boler\u2010Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute University of Notre Dame  Notre Dame Indiana USA"},{"name":"Department of Urology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boler\u2010Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute University of Notre Dame  Notre Dame Indiana USA"},{"name":"Department of Urology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackson","family":"Mittlesteadt","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boler\u2010Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-6478","authenticated-orcid":false,"given":"Xin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boler\u2010Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute University of Notre Dame  Notre Dame Indiana USA"},{"name":"Integrated Biomedical Sciences Graduate Program University of Notre Dame  Notre Dame Indiana USA"},{"name":"Tumor Microenvironment and Metastasis Program Indiana University Melvin and Bren Simon Cancer Center  Indianapolis Indiana 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