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For mutation assays, a site specific DSB was generated by the transient expression of a zinc finger nuclease which targets the human HPRT1 gene. A cell line in which time and site specific DSBs can be generated in a HR reporter construct was used for homology-directed repair (HR) analysis. By using these two systems, we investigated the effects of PI3-kinase inhibitors on the efficiency and quality of DSB repair. Ataxia telangiectasia mutated (ATM) kinase inhibition resulted a decrease in mutant frequency and a slight increase in deletion-type mutations accompanied by microhomology. Furthermore, the HR frequency increased significantly when ATM kinase activity was inhibited. Thus, ATM kinase activity might be involved in the suppression of DSB end resection, and this may promote DSB repair through canonical non-homologous end joining.<\/jats:p>","DOI":"10.1093\/rpd\/ncae074","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T11:31:38Z","timestamp":1731583898000},"page":"1598-1602","source":"Crossref","is-referenced-by-count":1,"title":["Effect of PI3-kinase inhibitors on DNA double strand break repair pathways: observations using a site specific DSB induction system"],"prefix":"10.1093","volume":"200","author":[{"given":"Tomoki","family":"Myodo","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Ibaraki University , Bunkyo 2-1-1, Mito 310-8512, Ibaraki,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ibaraki University , Bunkyo 2-1-1, Mito 310-8512, Ibaraki,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ibaraki University , Bunkyo 2-1-1, Mito 310-8512, Ibaraki,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honami","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ibaraki University , Bunkyo 2-1-1, Mito 310-8512, Ibaraki,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenta","family":"Iijima","sequence":"additional","affiliation":[{"name":"Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine , Handayama 1-20-1, Higashi-ku, Hamamatsu 431-3192, Shizuoka,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenshi","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Radiation Biology Center, Kyoto University , Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine , Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4934-2944","authenticated-orcid":false,"given":"Hiroshi","family":"Tauchi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ibaraki University , Bunkyo 2-1-1, Mito 310-8512, Ibaraki,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"2024111411310407400_ref1","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1259\/bjr.20130685","article-title":"DNA DSB repair pathway choice: an orchestrated handover mechanism","volume":"87","author":"Kakarougkas","year":"2014","journal-title":"British J. 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