Identification of Chromosome Inheritance Modifiers in Drosophila melanogaster

• Published in: Genetics (Austin) Vol. 157; no. 4; pp. 1623 - 1637
• Main Authors: Dobie, Kenneth W, Kennedy, Cameron D, Velasco, Vivienne M, McGrath, Tory L, Weko, Juliani, Patterson, Ryan W, Karpen, Gary H
• Format: Journal Article
• Language: English
• Published: United States Genetics Soc America 01.04.2001; Genetics Society of America
• Subjects: Animals; centrosomin (cnn) gene; Checkpoint Kinase 1; Cytoskeletal Proteins; DNA Transposable Elements; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila Proteins; Eukaryotic Initiation Factor-4E; Eye Proteins - genetics; Female; Genes; Genes, Insect; Glycoproteins - genetics; GTPase-activating protein 1 (Gap1) gene; Histones - genetics; Homeodomain Proteins - genetics; Insect Proteins - genetics; Male; Membrane Glycoproteins - genetics; Microfilament Proteins; Microtubule-Associated Proteins - genetics; minichromosomes; Mutation; pavarotti (pav) gene; Peptide Initiation Factors - genetics; Protein Kinases - genetics; rab5 GTP-Binding Proteins - genetics; ras GTPase-Activating Proteins - genetics; replication factor complex 4 (rfc4) gene; RNA-Binding Proteins; Trans-Activators - genetics; Transcription Factors; transposon P; wings apart-like (wap1) gene
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1093/genetics/157.4.1623

Faithful chromosome inheritance is a fundamental biological activity and errors contribute to birth defects and cancer progression. We have performed a P-element screen in Drosophila melanogaster with the aim of identifying novel candidate genes involved in inheritance. We used a "sensitized" minichromosome substrate (J21A) to screen approximately 3,000 new P-element lines for dominant effects on chromosome inheritance and recovered 78 Sensitized chromosome inheritance modifiers (Scim). Of these, 69 decreased minichromosome inheritance while 9 increased minichromosome inheritance. Fourteen mutations are lethal or semilethal when homozygous and all exhibit dramatic mitotic defects. Inverse PCR combined with genomic analyses identified P insertions within or close to genes with previously described inheritance functions, including wings apart-like (wapl), centrosomin (cnn), and pavarotti (pav). Further, lethal insertions in replication factor complex 4 (rfc4) and GTPase-activating protein 1 (Gap1) exhibit specific mitotic chromosome defects, discovering previously unknown roles for these proteins in chromosome inheritance. The majority of the lines represent mutations in previously uncharacterized loci, many of which have human homologs, and we anticipate that this collection will provide a rich source of mutations in new genes required for chromosome inheritance in metazoans.