Chromosome instability (CIN), involving the unequal distribution of DNA to daughter cells upon mitosis, is observed in the majority of solid tumors. The precise role of CIN in tumor development is uncertain but it may be an important predisposing factor for oncogenic progression by increasing the likelihood of tumor suppressor loss, gene copy number changes or translocations 
. Perhaps unsurprisingly, given the shared properties of eukaryotic mitoses, many known CIN genes belong to cellular pathways or structures conserved from yeast to humans (e.g. BUB1
, Aurora Kinase) 
. Mutations that cause CIN may drive tumor formation and progression 
. Although high-throughput screens for genome integrity are becoming a reality in human cells, the spectrum of human mutations that lead to CIN in tumors is only partially characterized 
. An ideal role for model organism genetics then would be to identify all cellular processes whose disruption can lead to a CIN phenotype, thus enabling identification and functional studies of candidate genes to focus on particular mutations among those found in a tumor genome.
Most functional genomic screens in yeast have naturally focused on the ~80% of yeast genes that are non-essential. Indeed, the yeast knockout collection is one of the most valuable genomic resources available. Several collections are now available to assay the functions of essential genes; each allele collection has advantages and disadvantages and only a handful of phenotypic screens have interrogated these collections 
. Previous CIN screens of non-essential gene deletions have catalogued the increased frequency of chromosome transmission fidelity (CTF), A-like faker (ALF), Bi-mater (BiM), loss of heterozygosity (LOH), and gross-chromosomal rearrangements (GCR) phenotypes 
. All of these phenotypes are considered CIN phenotypes as measured by an increase in the rate of marker loss although the mechanisms predominant in each assay differ. Since non-essential genes have been saturated with genome instability screens, a comprehensive screen of essential genes would create a high quality list of eukaryotic genome integrity pathways.
Here we investigate CIN phenotypes in ~2000 alleles of 1038 essential genes. When combined with published data for non-essential genes this resource defines yeast genome integrity pathways involving 692 genes and 387 enriched gene ontology (GO) terms. Using sequence orthology and the enriched GO terms to delineate CIN pathways, our data creates a list of cross species candidate human CIN genes. In principle, the yeast CIN gene catalogue described here comprises all conserved eukaryotic genome integrity pathways. Cross-referencing the derived human candidate CIN gene list with somatic mutations in human cancer reveals hundreds of CIN candidates mutated in tumors. Moreover, since tumor genomes typically contain many mutations this reference list of candidate CIN genes could help prioritize functional testing of novel somatic variants.
The CIN gene list also provides biological insights at the level of genome integrity pathways and individual CIN genes. As an example, we conduct a directed secondary screen for telomere length in poorly characterized essential CIN mutant strains. We identify four novel telomere modulators including two subunits of the ASTRA (ASembly of Tel, Rvb and Atm-like kinase) complex, TTI1
and ASA1 
. ASTRA is an essential seven-subunit protein complex with a proposed role in chromatin biology 
. Recent work highlights functional interactions among ASTRA subunits in metazoans; namely the TTT complex (Tel2-Tti1-Tti2) and the R2TP (Rvb1/2, Tah1, Pih1) complex which together affect biogenesis of phosphoinositide-3 kinase related kinase (PIKK) complexes 
. Therefore, ASTRA likely represents the interaction between yeast TTT, R2TP (or at least Rvb1/2) and a substrate PIKK. Our phenotypic analysis suggests that Asa1p functions with TTT to direct the biogenesis of PIKKs. Genome-wide phenotypic profiling of double mutants by synthetic genetic array (SGA) reveals strong TORC1 defects in TTT-ASA1
mutants which are likely due to reduced TOR-protein levels. Our data suggest that TTT function is conserved in yeast, and that its uncharacterized interacting partner, Asa1p, functions in the TTT pathway.