Clonogenic survival of WiDr cells transfected with siCON1, siCHK1 or siMYT1, with colonies counted after 10 days of MK-1775 exposure. The number of colonies was normalised to untreated controls for each siRNA separately (clonogenic survival before normalisation in the absence of MK-1775: siCON1: 69%, siMYT1: 67% and siCHK1: 35%). Knockdown of CHK1 and MYT1 was confirmed by Western blot (β-Actin, loading control).
B. Flow cytometry analysis of γH2AX and pH3 after transfection with siCON1, siCHK1 and siMYT1. Cells were exposed to 200 nM MK-1775 for the indicated times. γH2AXhighpH3+ cells represent unscheduled mitosis. Error bars represent SEM of two independent experiments.
C. Immunofluorescence images showing induction of pan-nuclear γH2AX (green) and pH3 (red) staining in WiDr cells transfected with siCON1, siCHK1 or siMYT1 and exposed to 300 or 600 nM MK-1775 for 8 hours. Double γH2AX+pH3+ staining (yellow) indicates premature mitosis. DNA was counterstained with DAPI (blue).
D. WiDr cells transfected with siCON1 (black bars) or siMYT1 (grey bars) were exposed to 250 nM MK-1775 for the indicated times. Cells were stained for γH2AX and imaged by confocal microscopy. Representative immunofluorescence images show premature mitotic cells (indicated by arrows) after 24 hours of MK-1775 exposure. Bar charts show number of γH2AX-positive cells (left), γH2AX intensity (middle) and premature mitosis (right) in siMYT1-transfected cells compared to siCON1. Error bars are SEM of two independent experiments.