Identification of chromosome inheritance modifiers in Drosophila melanogaster

Faithful chromosome inheritance is a fundamental biological activity and er rors contribute to birth defects and cancer progression. We have performed a P-element screen in Drosophila melanogaster with the aim of identifying n ovel candidate genes involved in inheritance. We used a "sensitized" minich romosome substrate (J21A) to screen similar to3.000 new P-element lines for dominant effects oil chromosome inheritance and recovered 78 Sensitized ch romosome inheritance modifiers (Scim). Of the st. 69 decreased minichromoso me inheritance while 9 increased minichromosome inheritance. Fourteen mutat ions are lethal or semilethal when homozygous and all exhibit dramatic mito tic defects. Inverse PCR combined with genomic analyses identified P insert ions within or close to genes with previously described inheritance functio ns, including wings apart-like (wapl), centrosomin (cnn), and pavarotti (pa v) Further. lethal insertions in replication factor complex 4 (rfc4) and GT Pase-activating protein I (Gap1) exhibit specific mitotic chromosome defect s, discovering previously unknown roles for these proteins in chromosome in heritance. The majority of tile lines represent mutations ill previously un characterized loci, many of which have human homologs, and we anticipate th at tills collection will provide a rich source of mutations in new genes re quired for chromosome inheritance ill metazoans.