Talk:CH391L/S2013 Alesha Stewart Feb 13 2013

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  • Logan Myler I was wondering about localization of the interaction between these two proteins. Parkin is a primarily mitochondrial protein, PCNA has been implicated to move from the nucleus to the cytoplasm for some of its functions, and DNA repair occurs in the nucleus. Because they said that Parkin does not ubiquitinate PCNA, can you speculate on the function of the interaction between the two and in what compartment this interaction might be localized?
    • Alesha Stewart When there is DNA damage parkin is translocated to the nucleus for the PCNA interaction. This study suggests DNA damage induces the translocation and that parkin is required for DNA repair [1]. I am not sure of the exact function between the two proteins-- involvement in recruitment for the initiation of DNA repair.

1. Kao, Shyan-Yuan. DNA damage induces nuclear translocation of parkin. Journal of Biomedical Science 16, 67 (2009).

  • Tanya R Parkin deletion has been shown to cause mitochondrial dysfunction which leads to an increase in reactive oxygen species (ROS). Increased levels of ROS causes increased DNA damage. [1,2]

Bearing that in mind, the authors observe that parkin null cells have lower survival rates, and higher levels of DNA damage (observed by histological staining). Both of these observations can be explained by the mitochondrial dysfunction that is incurred upon parkin deletion.

This leaves the reporter plasmid assay in which parkin +/+ cells are shown to be better able to repair DNA damage than those without parkin. Do you think that this observation reflects parkin as an active participant of the DNA damage response (DDR) or is this just a result of parkin null cells having increased ROS that causes a cycle of breakage and repair of the luciferase reporter which might explain the reduction in signal?

Do you have any suggestions for a good plan of action to understand the molecular pathways by which parkin may regulate the DDR?

1. Mortiboys, H., et al. (2008). "Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts." Annals of Neurology 64(5): 555-565. 2. Kuroda, Y., et al. (2006). "Parkin affects mitochondrial function and apoptosis in neuronal and myogenic cells." Biochemical and Biophysical Research Communications 348(3): 787-793.