A genome-wide screen in the yeast diploid deletion collection identifies 209 doxorubicin resistance genes enriched for those that show cross sensitivity to zymocin, ionizing radiation, loss of G1 size control and oxidative damage.

1Resistance to the G1 specific toxin zymocin was determined in a screen that was performed in parallel to that for the identification of DOX resistance mutants. A total of 806 diploid deletion strains (16.6% of nonessential genes) were found to be hypersensitive to zymocin. A total of 106 DOXS deletion mutants (50.7%) were found to be cross sensitive to the lethal effects of zymocin. This is 3 fold greater than that expected by chance alone.2A total of 204 ionizing radiation resistance genes (4% of nonessential genes) were identified in the diploid deletion collection as previously described [40], [39]. A total of 59 DOXS deletions (28.6%) were found to overlap with those that were identified as IR resistance genes. This is 7 fold greater than that expected by chance alone and suggests that DSBs are a significant component of the spectrum of lesions induced by DOX in S. cerevisiae.3Approximately 500 gene deletions (��10% of nonessential genes) in the haploid deletion collection were found to significantly affect cell size control that is determined in G1 and regulated by the checkpoint at ��START�� [43], [44]. A total of 74 DOX sensitive mutants (35.4%) were found to overlap with those that affect cell size control. This is 3.5 fold greater than that predicted by chance alone.4A total of 456 deletion mutants in the haploid deletion collection (9.4% of nonessential genes) were identified that demonstrated enhanced sensitivity to oxidative DNA damaging agents [60]. A total of 71 DOXS mutants (31%) were found to overlap with those determined to be sensitive to oxidative damage. This is 3.3 fold greater than that predicted by chance alone and suggests that oxidative damage lesions are a significant component of the spectrum of lesions.