Fig 1 Suppl Flow chart detailing the scoring

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Fig 1 Suppl Flow chart detailing the scoring system for the random spore analysis

Fig 1 Suppl Flow chart detailing the scoring system for the random spore analysis Colony from SPO plate resuspended in sterile distilled water Big colonies Small colonies (double mutants) CAN + G 418 CAN + NAT CAN + G 418 +NAT . . . Comparing the 6 plates (G 418, G 418+DOX, NAT+DOX, G 418+NAT+DOX) at 65 hrs CAN + G 418+DOX CAN + G 418 CAN + NAT+DOX CAN + NAT CAN + G 418 +NAT+DOX CAN + G 418 +NAT Synthetic Sick The colonies on all the plates (G 418, G 418+DOX, NAT+DOX, G 418+NAT) look normal but those on G 418+NAT+DOX are very small. . CAN + G 418+DOX . CAN + NAT+DOX . CAN + G 418 +NAT+DOX Synthetic lethal The colonies on all the plates (G 418, G 418+DOX, NAT+DOX, G 418+NAT) look normal but there are no colonies on G 418+NAT+DOX.

For strains that are slow on doxycycline Colony from SPO plate resuspended in sterile

For strains that are slow on doxycycline Colony from SPO plate resuspended in sterile distilled water 65 hrs CAN + G 418 CAN + NAT CAN + G 418 +NAT . . CAN + G 418+DOX CAN + G 418 CAN + NAT+DOX CAN + NAT CAN + G 418 +NAT+DOX No growth on CAN+G 418+DOX CAN Check plates every 24 hrs until well formed colonies seen on CAN+ G 418+DOX CAN + G 418 +NAT . . CAN + G 418+DOX . CAN + NAT+DOX . CAN + G 418 +NAT+DOX Synthetic lethal . .

TSC 11 SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg

TSC 11 SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox SD-His/Arg +canavanine +nat+dox SD-His/Arg +canavanine +G 418+nat +dox CDC 40 ts X tet 07 -PRP 38 CDC 40 ts X tet 07 -PRP 24

PRP 38 SD-His/Arg +canavanine CKS 1 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg

PRP 38 SD-His/Arg +canavanine CKS 1 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox SD-His/Arg +canavanine +nat+dox SD-His/Arg +canavanine +G 418+nat +dox CDC 40 ts X tet 07 -PRP 16 CDC 40 ts X tet 07 -CKS 1

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox SD-His/Arg +canavanine +nat+dox SD-His/Arg +canavanine +G 418+nat +dox CDC 40 ts X tet 07 -RTS 2 CDC 40 ts X tet 07 -RFA 2

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox SD-His/Arg +canavanine +nat+dox SD-His/Arg +canavanine +G 418+nat +dox CDC 40 ts X tet 07 -PSF 2 CDC 40 ts X tet 07 -TSC 11

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox SD-His/Arg +canavanine +nat+dox SD-His/Arg +canavanine +G 418+nat +dox CDC 40 ts X tet 07 -HSP 60 CDC 40 ts X tet 07 -KAP 95

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox SD-His/Arg +canavanine +nat+dox SD-His/Arg +canavanine +G 418+nat +dox CDC 40 ts X tet 07 -GPI 10 CDC 40 ts X tet 07 -GWT 1

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox

SD-His/Arg +canavanine +G 418 SD-His/Arg +canavanine +G 418+dox SD-His/Arg +canavanine +nat SD-His/Arg +canavanine+ nat+dox SD-His/Arg +canavanine +nat+dox SD-His/Arg +canavanine +G 418+nat +dox CDC 40 ts X tet 07 -YGL 047 W CDC 40 ts X tet 07 -FRQ 1