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Consequently, cells have evolved multiple mechanisms to efficiently repair DSBs to preserve genomic integrity. We have developed a DSB repair assay system, designated CDDR (CRISPR\u2013Cas9-based Dual-fluorescent DSB Repair), that enables the detection and quantification of DSB repair outcomes in mammalian cells with high precision. CDDR is based on the introduction and subsequent resolution of one or two DSB(s) in an intrachromosomal fluorescent reporter following the expression of Cas9 and sgRNAs targeting the reporter. CDDR can discriminate between high-fidelity (HF) and error-prone non-homologous end-joining (NHEJ), as well as between proximal and distal NHEJ repair. Furthermore, CDDR can detect homology-directed repair (HDR) with high sensitivity. Using CDDR, we found HF-NHEJ to be strictly dependent on DNA Ligase IV, XRCC4\u00a0and XLF, members of the canonical branch of NHEJ pathway (c-NHEJ). Loss of these genes also stimulated HDR, and promoted error-prone distal end-joining. Deletion of the DNA repair kinase ATM, on the other hand, stimulated HF-NHEJ and suppressed HDR. These findings demonstrate the utility of CDDR in characterizing the effect of repair factors and in elucidating the balance between competing DSB repair pathways.<\/jats:p>","DOI":"10.1093\/nar\/gkaa897","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T03:32:50Z","timestamp":1601523170000},"page":"e126-e126","source":"Crossref","is-referenced-by-count":19,"title":["A robust CRISPR\u2013Cas9-based fluorescent reporter assay for the detection and quantification of DNA double-strand break repair"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7007-4246","authenticated-orcid":false,"given":"Rebeka","family":"Eki","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Virginia, Charlottesville, VA\u00a022908, USA"},{"name":"Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA\u00a022908, USA"},{"name":"Center for Cell Signaling, University of Virginia, Charlottesville, VA\u00a022908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"She","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Virginia, Charlottesville, VA\u00a022908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Parlak","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Virginia, Charlottesville, VA\u00a022908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouadh","family":"Benamar","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Virginia, Charlottesville, VA\u00a022908, USA"},{"name":"Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA\u00a022908, USA"},{"name":"Center for Cell Signaling, University of Virginia, Charlottesville, VA\u00a022908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Ping","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Virginia, Charlottesville, VA\u00a022908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA\u00a022908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1398-6545","authenticated-orcid":false,"given":"Tarek","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Virginia, Charlottesville, VA\u00a022908, USA"},{"name":"Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA\u00a022908, USA"},{"name":"Center for Cell Signaling, University of Virginia, Charlottesville, VA\u00a022908, USA"},{"name":"Cancer Center, University of Virginia, Charlottesville, VA\u00a022908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,17]]},"reference":[{"key":"2020120119370933100_B1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.tcb.2015.07.009","article-title":"Repair pathway choices and consequences at the double-strand break","volume":"26","author":"Ceccaldi","year":"2016","journal-title":"Trends Cell Biol"},{"key":"2020120119370933100_B2","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41580-019-0152-0","article-title":"DNA double-strand break repair-pathway choice in somatic mammalian cells","volume":"20","author":"Scully","year":"2019","journal-title":"Nat. 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