PFM01 is a cell-permeable N-alkylated Mirin (Sigma Cat. No. 475954) derivative that selectively inhibits against MRE11 endo-, but not exo-, nuclease activity. PFM01 targets MRE11 at a site near the dimer interface, distinct from that occupied by Mirin and PFM39 to allow disruption of the ssDNA-binding groove and selective inhibition against MRE11 endo-, but not exo-, nuclease activity. While both endonuclease and exonuclease activities are required for MRE11-mediated homologous recombination (HR) repair, only FM01 (100 μM), but not the exonuclease inhibitors Mirin (500 μM) and PFM39 (100 μM), rescues G2-phase double-strand break (DSB) repair defect in HR protein BRCA2-deficient HSC62-hTERT fibroblasts following ionizing irradiation (IR) by blocking HR initiation and thereby allowing non-homologous end joining (NHEJ) to proceed.
PFM01 is a cell-permeable N-alkylated Mirin derivative that selectively inhibits against MRE11 endo-, but not exo-, nuclease activity.
Cell chemical biology, 24(9), 1101-1119 (2017-09-25)
To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop
Proceedings of the National Academy of Sciences of the United States of America, 118(11) (2021-03-13)
Homologous recombination (HR) is a major pathway for repair of DNA double-strand breaks (DSBs). The initial step that drives the HR process is resection of DNA at the DSB, during which a multitude of nucleases, mediators, and signaling proteins accumulates
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(2), 2812-2820 (2020-01-08)
The Mre11A/RAD50/NBN complex (MRN) is an essential regulator of the cellular damage response after DNA double-strand breaks (DSBs). More recent work has indicated that MRN may also impact on the duration of mitosis. We show here that RAD50-deficient fibroblasts exhibit
