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In contrast, single substitutions of the chromophore's \u03b2-amino acid component shifted DNA damage to primarily DSBs, consistent with its induction of conventional ATM-dependent damage responses of the type generated by ionizing radiation and other radiomimetics. Thus, phosphatidylinositol 3-kinase-like protein kinase regulation of DNA damage responses is dictated by the relative proportions of DSBs and ICLs.<\/jats:p>","DOI":"10.1073\/pnas.0708274104","type":"journal-article","created":{"date-parts":[[2007,10,31]],"date-time":"2007-10-31T21:17:43Z","timestamp":1193865463000},"page":"17632-17637","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["Designer enediynes generate DNA breaks, interstrand cross-links, or both, with concomitant changes in the regulation of DNA damage responses"],"prefix":"10.1073","volume":"104","author":[{"given":"Daniel R.","family":"Kennedy","sequence":"first","affiliation":[{"name":"*Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Ju","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences,"},{"name":"University of Wisconsin National Cooperative Drug Discovery Group, and"},{"name":"Department of Chemistry, University of Wisconsin, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry A.","family":"Beerman","sequence":"additional","affiliation":[{"name":"*Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263; 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