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 similar to3.000 new P-element lines for dominant effects oil chromosome inheritance and recovered 78 Sensitized chromosome inheritance modifiers (Scim). Of the st. 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 I (Gap1) exhibit specific mitotic chromosome defects, discovering previously unknown roles for these proteins in chromosome inheritance. The majority of the lines represent mutations ill previously uncharacterized loci, many of which have human homologs, and we anticipate that tills collection will provide a rich source of mutations in new genes required for chromosome inheritance ill metazoans.