Single cell tracking reveals that Msh2 is a key component of an early-acting DNA damage-activated G2 checkpoint
- Marquez, Nuria
- Chappell, Sally Claire
- Sansom, Owen J.
- Clarke, Alan Richard
- Errington, Rachel Jane
- Smith, Paul James
- Court, Jonathan
DOIAbstract
Dysfunction of cell-cycle checkpoints in DNA mismatch repair (MMR)-deficient cells in response to DNA damage has implications for anticancer therapy and genetic instability. We have studied the cell-cycle effects of MMR deficiency (Msh2-/-) in primary mouse embryonic fibroblasts (MEFs) exposed to cisplatin (10 M 1 h) using time-lapse microscopy. Kinetic responses of MEFs from different embryos and passage ages varied, but we report a consistent drug-induced inhibition of mitotic entry (approx. 50%). There was a loss of an early-acting (<5 h) delay in G2 to M transition in Msh2-/- cells, although a later-acting G2 arrest was apparently normal. This suggests that Msh2 primarily acts to delay mitotic entry of cells already in G2, that is, DNA...
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