Figure 1
Calculation of the rate of HAC miss-segregation induced by drug treatment. Justification of the algorithm describing the dynamics of the accumulation of HAC-less cells caused by a single dose of chromosome-destabilizing compounds. This mathematical model assumes: 1) the drug kills cells non-selectively; 2) the drug’s effect on HAC mis-segregation is not persistent and limited to the cell cycle when it is present; 3) spontaneous HAC loss after drug exposure does not change; 4) the HAC does not confer a selective advantage or disadvantage; 5) the cells are growing synchronously and 6) there is one HAC per cell. Assumptions 2) and 3) have been confirmed experimentally (see Additional file 1). (A) Our model assumes that when mis-segregation occurs during mitosis, one daughter cell will inherit a HAC while the other daughter cell does not. (B) Illustrated model of HAC lost in a population of cells. (C) Derivation of the general equation for HAC miss-segregation rate. x is the number of cells which are EGFP(+); y is the number of cell which are GFP(−); R is the probability of HAC miss-segregation; n is the number of cell divisions; P0 is the proportion of EGFP(+) cell at generation F0; P1 is the proportion of EGFP(+) cell at generation F1. (D) Calculation of rates (see Methods for more details).