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Analysis of &gt;2 million images, acquired by quantitative fluorescence microscopy, showed that depletion of 1,152 genes strongly affected cell-cycle progression. These genes clustered into eight distinct phenotypic categories based on phase of arrest, nuclear area, and nuclear morphology. Phase-specific networks were built by interrogating knowledge-based and physical interaction databases with identified genes. Genome-wide analysis of cell-cycle regulators revealed a number of kinase, phosphatase, and proteolytic proteins and also suggests that processes thought to regulate G\n            <jats:sub>1<\/jats:sub>\n            -S phase progression like receptor-mediated signaling, nutrient status, and translation also play important roles in the regulation of G\n            <jats:sub>2<\/jats:sub>\n            \/M phase transition. Moreover, 15 genes that are integral to TNF\/NF-\u03baB signaling were found to regulate G\n            <jats:sub>2<\/jats:sub>\n            \/M, a previously unanticipated role for this pathway. These analyses provide systems-level insight into both known and novel genes as well as pathways that regulate cell-cycle progression, a number of which may provide new therapeutic approaches for the treatment of cancer.\n          <\/jats:p>","DOI":"10.1073\/pnas.0604320103","type":"journal-article","created":{"date-parts":[[2006,9,26]],"date-time":"2006-09-26T01:03:54Z","timestamp":1159232634000},"page":"14819-14824","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":112,"title":["Genome-wide functional analysis of human cell-cycle regulators"],"prefix":"10.1073","volume":"103","author":[{"given":"Mridul","family":"Mukherji","sequence":"first","affiliation":[{"name":"*The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 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