While mitochondrial DNA ligase III-alpha also interacts with XRCC1, it is likely that the activity of the mitochondrial targeting sequence of DNA ligase III-alpha is greater than the activity of the XRCC1 nuclear localization signal and that the DNA ligase III-alpha/XRCC1 complex is disrupted when mitochondrial DNA ligase III-alpha passes through the mitochondrial membrane.
Aínda que a ADN ligase III-alfa mitocondrial tamén interacciona con XRCC1, é probable que a actividade da secuencia de destino mitocondrial da ADN ligase III-alfa sexa maior que a actividade do sinal de localización nuclear da XRCC1 e que o complexo ADN ligase III-alfa/XRCC1 sexa alterado cando a ADN ligase III-alfa mitocondrial pasa a través da membrana mitocondrial.