p53

1. Origanti_Fig S1 p21 null A WT p53 null - - Irinotecan - + + - + + - - - - + + + + UCN-01 p53 GAPDH 1 2 3 4 5 6 7 8 9 B p53 null WT - - - + + - + + Irinotecan - - - - + + UCN-01 + + p21 Tubulin 1 2 3 4 5 6 7 8 C ** Irinotecan 80 Irinotecan – UCN-01 ** 60 * *** Cleaved PARP positive cells per 50 crypts 40 20 0 D p53/p21 null p21 null p53 null WT 50 * Vehicle 40 AZD7762 Irinotecan ** Irinotecan – AZD7762 30 CC3 positive cells per 50 crypts 20 10 0 p53 null WT p21 null

2. Origanti_Fig S2 Irinotecan Vehicle A WT p53 null p21 null 100μM B Vehicle ** ** 40 Irinotecan 30 Percent BrdU positive 20 10 0 p53 null WT p21 null

3. Origanti_Fig S3 A Merge DAPI CC3 pHH3 20μM B ** ** * % co-stained for pHH3 and CC3 Vehicle p21 null WT p53 null p53/p21 null UCN-01 Irinotecan C Irinotecan - UCN-01 D 8 Purvalanol A Vehicle 100 ** * 6 p53 null 80 60 4 pHH3 positive cells per 75 crypts 40 2 p21 null 20 0 0 p21 null p53 null

4. Origanti_Fig S4 B A 0 2 3 1 3 Percent strength of γH2AX intensity 100 µM Irinotecan-UCN-01 Vehicle UCN-01 Irinotecan p53/p21 null C D 40 Vehicle Vehicle Irinotecan Irinotecan 30 Percent BrdU positive 20 p53/ p21 null 10 0 p53/p21 null E F p21 / 14-3-3 null p21 sh clone #3 Ctrl sh p21 sh clone #28 p21 sh clone #26 p21 sh clone # 25 p21 / 14-3-3 null p21 sh#1 p21 sh#3 (1) Mock p21 sh#2 p21 sh#3 (2) p53 p53 p21 p21 Tubulin Tubulin 1 2 3 4 5 6 1 2 3 4 5 6

5. Origanti_Fig S5 B A p21 shRNA+ p21 rescue Ctrl shRNA p21 shRNA Irinotecan Irinotecan – AZD7762 p21 p53 null p21 KD + p21 rescue Tubulin 100μM 1 2 3 25 20 Vehicle C AZD7762 Irinotecan Irinotecan – AZD7762 15 10 * 5 0 ns % CC3 positive p53 null p21KD + p21 Parental p53 null p53 null p21KD