title: Single-Cell Based Quantitative Assay of Chromosome Transmission Fidelity.
abstract: Errors in mitosis are a primary cause of chromosome instability (CIN), generating aneuploid progeny cells. Whereas a variety of factors can influence CIN, under most conditions mitotic errors are rare events that have been difficult to measure accurately. Here we report a green fluorescent protein-based quantitative chromosome transmission fidelity (qCTF) assay in budding yeast that allows sensitive and quantitative detection of CIN and can be easily adapted to high-throughput analysis. Using the qCTF assay, we performed genome-wide quantitative profiling of genes that affect CIN in a dosage-dependent manner and identified genes that elevate CIN when either increased (icCIN) or decreased in copy number (dcCIN). Unexpectedly, qCTF screening also revealed genes whose change in copy number quantitatively suppress CIN, suggesting that the basal error rate of the wild-type genome is not minimized, but rather, may have evolved toward an optimal level that balances both stability and low-level karyotype variation for evolutionary adaptation.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110.
authors.forename: Dominic
authors.initials: D
authors.lastname: Heinecke
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160.
authors.forename: Wahid A
authors.initials: WA
authors.lastname: Mulla
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110.
authors.forename: William D
authors.initials: WD
authors.lastname: Bradford
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110.
authors.forename: Boris
authors.initials: B
authors.lastname: Rubinstein
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110.
authors.forename: Andrew
authors.initials: A
authors.lastname: Box
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Haug
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160 rli@stowers.org.
authors.forename: Rong
authors.identifier: http://orcid.org/0000-0002-1185-7283
authors.initials: R
authors.lastname: Li
mesh_terms: D043171:Chromosomal Instability / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics*; D005453:Fluorescence; D018628:Gene Dosage; D020869:Gene Expression Profiling; D016153:Genes, Suppressor; D016681:Genome, Fungal; D016366:Open Reading Frames / Q000235:genetics; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D059010:Single-Cell Analysis / Q000379:methods*
keywords: chromosome instability; dosage-sensitive gene; mitosis; qCTF assay
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