Systems modelling of NHEJ reveals the importance of redox regulation of Ku70/80 in the dynamics of dna damage foci.

ABSTRACT: The presence of DNA double-stranded breaks in a mammalian cell typically activates the Non-Homologous End Joining (NHEJ) pathway to repair the damage and signal to downstream systems that govern cellular decisions such as apoptosis or senescence. The signalling system also stimulates effects such as the generation of reactive oxygen species (ROS) which in turn feed back into the damage response. Although the overall process of NHEJ is well documented, we know little of the dynamics and how the system operates as a whole. We have developed a computational model which includes DNA Protein Kinase (DNA-PK) dependent NHEJ (D-NHEJ) and back-up NHEJ mechanisms (B-NHEJ) and use it to explain the dynamic response to damage induced by different levels of gamma irradiation in human fibroblasts. Our w

SUBMITTER: Dolan D 

PROVIDER: S-EPMC3566652 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature