Hamster EM9 cells, which lack Xrcc1 protein, have reduced levels of DNA ligase lll and defective in nuclear base excision repair. The Xrcc1 protein stabilizes DNA ligase lll and may even play a direct role in catalyzing base excision repair. Since DNA ligase lll is also thought to function in mitochondrial base excision repair, it seemed likely that mitochondrial DNA ligase lll function would also be dependent upon Xrcc1. However, several lines of evidence indicate that this is not the case. First, western bolt analysis failed to detect Xrcc1 protein in mitochondrial extracts. Second, DNA ligase lll levels present in mitochondrial protein extracts from EM9 cells were indistinguishable from those seen in similar extracts from wild-type (AAB) cells. Third, the mitochondrial DNA content of both cell lines was idetical. Fourth, EM9 cells displayed no defect in their ability to repair spontaneous mitochondrial DNA damage. Fifth, while EM9 cells were far more sensitive to the cytotoxic effects of ionizing radiation due to a defect in nuclear DNA repair, there was no apparent difference in the ability of EM9 and AA8 cells to restore their mitochondrial DNA to pre-irradiation levels. Thus, mitochondrial DNA ligase lll function is independent of the Xrcc1 protein.
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