Of 30 mutants tested, 24 demonstrated enhanced sensitivity to doxorubicin as both a diploid and an isogenic haploid when compared to the repair competent WT strains.
Such a profile of induction and repair is typical of many repair competent cells (e.g., reference 11).
For example, what is the molecular mechanism that facilitates telomere fusion in DSB repair competent mitotic cells?
In the repair competent MRC5-SV1 cells, there is a dramatic induction of nuclear fluorescence (γ-H2AX) foci at 30 min post 2 Gy gamma irradiation.
If overhangs are removed from metaphase-TIF as a general phenomenon this may also contribute to telomere fusions in DSB repair competent mitotic cells.
Which in DSB repair competent mitotic cells would result in more sister-telomere fusions despite the initial induction of non-specific genome wide damage.
In the same study, we also show that repair competent cell lines differing widely in radiosensitivity repair 94 98% of their damaged DNA within 12 h with no apparent correlation between residual damage and radiosensitivity.
However, a likely answer is that intermediate-state telomeres, which normally suppress NHEJ during interphase, fuse during cell division in DSB repair competent mitotic cells (i.e. in a RNF8 T198andnd 53BP1 TASA over-expression background) (Fig. 3).
This confirmed that 4 is the most potent cytotoxin in the repair-defective UV4 cell line, but unexpectedly was 11 70-fold 11 70-foldt in the four repair competent celessines tested.
For the repair competent MRC5-SV1 cells, there is a rapid and predictable induction of γ-H2AX foci detected at 30 min postirradiation (Fig. 3A) followed by repair of the DSB and loss of γ-H2AX foci.
Moreover, Orthwein et al. 3 found irradiation of DSB repair competent mitotic cells resulted in increased metaphase-TIF and greater numbers of sister-telomere fusions, both of which were Hesperadin sensitive.
