PT  - JOURNAL ARTICLE
AU  - J. Javier Díaz-Mejía
AU  - Albi Celaj
AU  - Joseph C. Mellor
AU  - Atina Coté
AU  - Attila Balint
AU  - Brandon Ho
AU  - Pritpal Bansal
AU  - Fatemeh Shaeri
AU  - Marinella Gebbia
AU  - Jochen Weile
AU  - Marta Verby
AU  - Anna Karkhanina
AU  - YiFan Zhang
AU  - Cassandra Wong
AU  - Justin Rich
AU  - D’Arcy Prendergast
AU  - Gaurav Gupta
AU  - Sedide Öztürk
AU  - Daniel Durocher
AU  - Grant W. Brown
AU  - Frederick P. Roth
TI  - Mapping DNA damage-dependent genetic interactions in yeast via party mating and barcode fusion genetics
AID  - 10.1101/181750
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 181750
4099  - http://biorxiv.org/content/early/2018/05/02/181750.short
4100  - http://biorxiv.org/content/early/2018/05/02/181750.full
AB  - Condition-dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State-of-the-art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double mutant strains, does not scale readily to multi-condition studies. Here we describe Barcode Fusion Genetics to map Genetic Interactions (BFG-GI), by which double mutant strains generated via en masse ‘party’ mating can also be monitored en masse for growth and genetic interactions. By using site-specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG-GI enables multiplexed quantitative tracking of double mutants via next-generation sequencing. We applied BFG-GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4NQO), bleomycin, zeocin, and three other DNA-damaging environments. BFG-GI recapitulated known genetic interactions and yielded new condition-dependent genetic interactions. We validated and further explored a subnetwork of condition-dependent genetic interactions involving MAG1, SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to a decrease in the activation or activity of the checkpoint protein kinase Rad53.