Alkylation DNA damage in combination with PARP inhibition results in formation of S-phase-dependent double-strand breaks.

@article{Heacock2010AlkylationDD,
  title={Alkylation DNA damage in combination with PARP inhibition results in formation of S-phase-dependent double-strand breaks.},
  author={Michelle L. Heacock and Donna F. Stefanick and Julie K. Horton and Samuel Hodin Wilson},
  journal={DNA repair},
  year={2010},
  volume={9 8},
  pages={
          929-36
        }
}
The combination of poly(ADP-ribose)polymerase (PARP) inhibitors and alkylating agents is currently being investigated in cancer therapy clinical trials. However, the DNA lesions producing the synergistic cell killing effect in tumors are not fully understood. Treatment of human and mouse fibroblasts with the monofunctional DNA methylating agent methyl methanesulfonate (MMS) in the presence of a PARP inhibitor has been shown to trigger a cell cycle checkpoint response. Among other changes, this… CONTINUE READING
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