Development of General Methods for Identification of Genes Regulated by Oncogenic Stimuli or DNA Damage

摘要

In order for cells to prevent mutations, they have an elaborate regulatory network that is capable of sensing and responding to chromosomal aberrations. When damage to chromosomes is detected, cells induce a set of genes that respond to the damage in order to repair the damage and to prevent the cell cycle from progressing. In addition, cells have set up another elaborate regulatory network to ensure that the key events of the cell cycle occur in the correct order with the correct timing. Both the DNA damage response and the cell cycle regulatory pathways are critical to prevent the types of events that generate cancers. Furthermore, both of these pathways operate by the precise regulation of transcription of genes involved in this process. Our proposal has centered around identification of DNA damage inducible genes and genes important in the cell cycle by either retroviral insertions or, more recently by microarray hybridization. We have now identified several hundred genes regulated by these events, either DNA damage or the cell cycle and have learned a great deal about the processes the cell employes to prevent the accumulation of cancer-causing mutations.