Identification of chromosome inheritance modifiers in Drosophila melanogaster.
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.
Dobie
K W
KW
Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Kennedy
C D
CD
Velasco
V M
VM
McGrath
T L
TL
Weko
J
J
Patterson
R W
RW
Karpen
G H
GH
D000818:Animals; D000071877:Checkpoint Kinase 1; D003598:Cytoskeletal Proteins; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D039561:Eukaryotic Initiation Factor-4E; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D017344:Genes, Insect; D006023:Glycoproteins / Q000235:genetics; D006657:Histones / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D016601:RNA-Binding Proteins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D020696:rab5 GTP-Binding Proteins / Q000235:genetics; D020703:ras GTPase-Activating Proteins / Q000235:genetics
D003598:Cytoskeletal Proteins; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D005136:Eye Proteins; D006023:Glycoproteins; D006657:Histones; D018398:Homeodomain Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; C491146:RasGAP1 protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; C107943:bif protein, Drosophila; C098130:cnn protein, Drosophila; C499600:dom protein, Drosophila; C490516:pav protein, Drosophila; C026742:plastin; D020703:ras GTPase-Activating Proteins; C066579:sca protein, Drosophila; C070574:nos protein, Drosophila; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; D020696:rab5 GTP-Binding Proteins