Measuring the effect of environmental stress on cell survival during replication stress

DNA replication checkpoint ensures cell fitness under replication stress by restraining fork progression and arresting cell cycle. Without checkpoint proteins, cells die in a replication inhibitor hydroxyurea (HU). However, cellular environment may affect their survival in HU. Therefore, the main goal of this study was to examine the effect of environmental stress and to study how it promotes survival in replication checkpoint mutants of fission yeast (rad3∆, mrc1∆, cds1∆). Our viability assays showed a significant increase in these mutants survival in heat-shock + HU compared to HU alone. Cell-cycle staging suggests that cells are altered after heat shock, affecting their response to HU. We measured the consequences to this enhanced survival and found that surviving population exhibits altered DNA mis-segregation and mutation rate. Collectively, our work points to a general cellular response to various environmental stressors that affects survival under replication stress, and may be applicable to human disease.