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Because the FRT and lox target sites for the commonly used FLP and Cre recombinases are asymmetrical, and must pair in the same direction to recombine, construct design must take into account orientation of the target sites. Both direct and inverted configurations have been used. However, the outcome of recombination between target sites on sister chromatids is frequently overlooked. This is especially consequential with inverted target sites, where exchange between oppositely oriented target sites on sisters will produce dicentric and acentric chromosomes. By using constructs that have inverted target sites in Drosophila melanogaster and in mice, we show here that dicentric chromosomes are produced in the presence of recombinase, and that the frequency of this event is quite high. The negative effects on cell viability and behavior can be significant, and should be considered when using such constructs.<\/jats:p>","DOI":"10.1534\/genetics.120.303394","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T22:15:27Z","timestamp":1593123327000},"page":"923-930","source":"Crossref","is-referenced-by-count":6,"title":["Site-Specific Recombination with Inverted Target Sites: A Cautionary Tale of Dicentric and Acentric Chromosomes"],"prefix":"10.1093","volume":"215","author":[{"given":"Simon W A","family":"Titen","sequence":"first","affiliation":[{"name":"Eccles Institute of Human Genetics, School of Medicine, University of Utah, Salt Lake City, Utah, 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makenna T B","family":"Johnson","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Utah, Salt Lake City, Utah, 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Capecchi","sequence":"additional","affiliation":[{"name":"Eccles Institute of Human Genetics, School of Medicine, University of Utah, Salt Lake City, Utah, 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kent G","family":"Golic","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Utah, Salt Lake City, Utah, 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"2022011800200498600_bib1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/genetics\/148.2.775","article-title":"The transmission of fragmented chromosomes in Drosophila melanogaster.","volume":"148","author":"Ahmad","year":"1998","journal-title":"Genetics"},{"key":"2022011800200498600_bib2","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1093\/genetics\/151.3.1041","article-title":"Telomere loss in somatic cells of Drosophila causes cell cycle arrest and apoptosis.","volume":"151","author":"Ahmad","year":"1999","journal-title":"Genetics"},{"key":"2022011800200498600_bib3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1249252","article-title":"Total synthesis of a functional designer eukaryotic chromosome.","volume":"344","author":"Annaluru","year":"2014","journal-title":"Science"},{"key":"2022011800200498600_bib4","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.ydbio.2019.05.006","article-title":"Multicolor lineage tracing using in vivo time-lapse imaging reveals coordinated death of clonally related cells in the developing vertebrate brain.","volume":"453","author":"Brockway","year":"2019","journal-title":"Dev. 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