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Research Paper
Genetic Response to DNA Damage: Proapoptotic Targets of RhoB Include Modules for p53 Response and Susceptibility to Alzheimer’s Disease
Uma Kamasani and George C. Prendergast
volume 4 | issue 3
march 2005Pages: 282-288
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Knockout mouse studies indicate that the small GTPase RhoB is critical for apoptosis triggered by genotoxic stress in transformed mouse cells. However, the mechanisms used by RhoB to sensitize cells to cell death are obscure. To gain insight into this question, we compared the genetic response of cells with different rhoB genotypes to the DNA damaging anticancer drug doxorubicin (DOX). The microarray hybridization strategy focused on events occurring by 6 hr of DOX treatment, preceding the execution phase of RhoB-dependent apoptosis by 12-16 hr. Genes controlling cytoskeletal organization, adhesion, transcription, trafficking, apoptosis, and protein turnover were represented prominently. Gene clustering revealed a module of p53 target genes, suggesting that RhoB may modify the p53 response, and a module for susceptibility to Alzheimer’s disease, suggesting a link between RhoB and age-associated dementia. The findings of this study suggest mechanisms by which RhoB may act to elevate the sensitivity of cells to apoptosis following genotoxic stress.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.