Deficient HR causes sensitivity to ionizing radiation.
SIRT6 deficient cells display sensitivity to oxidative stress and a reduced capacity for DNA repair, while SIRT6 knockout mice show many hallmarks of premature aging [ 36].
Similar to several other lysosomal storage diseases (36, 37), saposin C deficient mice showed sensitivity of Purkinje cells to the disease state.
Finally, the GBM U87 cell line, which is MMR-proficient and MGMT-deficient, showed higher sensitivity in comparison with the MMR-deficient SJGBM-2 cell line.
A differential response of cells with proficient- and deficient-MLH1 in sensitivity to cisplatin and 6-TG in ovarian cells was observed in this study.
We report that MMR-deficient cells retain sensitivity to brostallicin, thereby extending the list of potential anticancer agents for use in the treatment of MMR-deficient tumours, and that brostallicin-induced cytotoxicity may not require ATM and DNA-PK.
In contrast to earlier reports, however, this is not required for the induction of apoptosis since the overexpression of cleavage-resistant Cas mutants in Cas-deficient MEFs increases sensitivity to MG132.
At this threshold, our markers detected 40 out of 41 tumors MMR-deficient on IHC (sensitivity ∼98%), while only 1 out of 184 MMR-normal tumors on IHC were identified as MSI (specificity > 99%).
These results are consistent with previous observations that PPARγ-deficient fibroblasts showed enhanced sensitivity to TGFβ1 and that PPARγ-deficient mice showed increased susceptibility to bleomycin-induced skin fibrosis [ 8, 9].
POLQ deficient mice show increased sensitivity to low doses of bleomycin in their bone marrow cells [ 20], and the same sensitivity has been observed in human tumor cells exposed to ionizing radiation [ 21].
