DNA damage-induced gene expression: Signal transduction and relation to growth factor signaling

In mammalian cells, as in bacteria, DNA-damaging agents induce over-replication and a new program of gene expression. An increasing number of induced proteins have been identified; still, most physiologic functions of stress-induced proteins are unknown. Elements of the regulatory mechanism have, however, been unraveled. DNA damage appears to be the major primary event. Transcription factors are posttranslationally modified. Some components of signal transfer have been identified: a growth factor loop delivers signals to the irradiated cell and to neighboring cells. With respect to long-lasting consequences of the DNA-damage response, an important observation concerns the DNA damage-induced increase in abundance of proteins that participate in the generation of mutations. These proteins can be upregulated by oncogenes in the absence of DNA damage. This process may be relevant for the mechanism of tumor promotion and tumor progression.