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Defects in ICL repair result in Fanconi anemia, which is characterized by bone marrow failure, developmental abnormalities, and a high incidence of malignancies. SLX4, also known as FANCP, acts as a scaffold protein and coordinates multiple endonucleases that unhook ICLs, resolve homologous recombination intermediates, and perhaps remove unhooked ICLs. In this study, we explored the role of SLX4IP, a constitutive factor in the SLX4 complex, in ICL repair. We found that SLX4IP is a novel regulatory factor; its depletion sensitized cells to treatment with ICL-inducing agents and led to accumulation of cells in the G2\/M phase. We further discovered that SLX4IP binds to SLX4 and XPF\u2013ERCC1 simultaneously and that disruption of one interaction also disrupts the other. The binding of SLX4IP to both SLX4 and XPF\u2013ERCC1 not only is vital for maintaining the stability of SLX4IP protein, but also promotes the interaction between SLX4 and XPF\u2013ERCC1, especially after DNA damage. Collectively, these results demonstrate a new regulatory role for SLX4IP in maintaining an efficient SLX4\u2013XPF\u2013ERCC1 complex in ICL repair.<\/jats:p>","DOI":"10.1093\/nar\/gkz769","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T19:27:28Z","timestamp":1567711648000},"page":"10181-10201","source":"Crossref","is-referenced-by-count":36,"title":["SLX4IP acts with SLX4 and XPF\u2013ERCC1 to promote interstrand crosslink repair"],"prefix":"10.1093","volume":"47","author":[{"given":"Huimin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrinal","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Tainer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"2019103013402666400_B1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s41021-016-0037-9","article-title":"Mechanisms of interstrand DNA crosslink repair and human disorders","volume":"38","author":"Hashimoto","year":"2016","journal-title":"Genes Environ."},{"key":"2019103013402666400_B2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/10409230903501819","article-title":"DNA interstrand crosslink repair in mammalian cells: step by step","volume":"45","author":"Muniandy","year":"2010","journal-title":"Crit. 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