DNA Crosslink-induced Transcriptional Changes in Mouse Embryonic Stem Cells

Genome maintenance is of the utmost importance in stem cells, as mutations can be propagated and cause defects in derivative tissues. Many stem cell types display low mutation rates, with embryonic stem cells (ESCs) being a notable example. The bases for this property are unclear but may be achieved by optimization of various processes including high-fidelity DNA repair, cell cycle checkpoint controls, and hypersensitivity to genotoxic insults that trigger cell death. Here, we investigate the transcriptional basis of the unique responses of mouse ESCs (mESCs) to replication stress (RS) using MMC. We find that whereas mESCs lack a strong G2/M checkpoint, they maintain a spindle assembly checkpoint (SAC). Overall design: Embryonic stem cells (V6.5) of the indicated genotypes (Fancm=fancm-/-, WT=Wild type) were treated with 150nM mitomycin C (MMC) or a vehicle control (NT) for 24 hours before harvest and RNA extraction. Each genotype/condition was repeated for 3 biological replicates.