Chapter Category: Gene Expression

From the book Microarrays and Transcription Networks

Transcriptional Responses to DNA Damage: Systems-Level Delineation by Functional Genomics

Ran Elkon, Sharon Rashi-Elkeles, Ron Shamir and Yosef Shiloh

The completion of genome sequencing in various organisms, together with the matura- tion of novel high-throughput biotechnologies and the development of powerful com- putational algorithms now allow the application of systems-level analysis to biological networks. Notable achievements of systems-biology have been in global delineation of transcriptional regulatory networks. These achievements were made possible by the rapid advance in gene expression microarray technologies and the ‘ChIP-on-chip’ technique, both of which shed light specifically on the transcriptome layer of cellular systems. Damage to the DNA poses one of the greatest threats to the function and life of the cell and the organism. Cellular responses to DNA damage have long been viewed mainly in terms of the concerted activation of DNA repair mechanisms and cell cycle checkpoints. However, studies that applied functional genomics techniques demonstrate that the damage-invoked network is much broader. These studies show that DNA damage sets off a wide array of signaling pathways that cover most aspects of cellular physiology, ranging from metabolic pathways to changes in protein turnover, cellular trafficking and cell-to-cell signaling. Functional genomics have greatly expanded our knowledge on DNA damage responses, although the biological significance of most of the newly-identified induced pathways remains unclear. Further research is needed to illuminate how the induction of these diverse pathways contributes to the ability of the organism to cope with the challenge of genotoxic stress. The utilization of functional genomics in the study of DNA damage is also expected to significantly improve our understanding of molecular factors that determine sensitivity of tumors to radiotherapy and DNA damage-based chemotherapies, spurring the development of improved cancer treatments. In this chapter we review several studies in which functional genomics approaches were applied to elucidate transcriptional networks that are induced in response to genotoxic stress.
  • ISBN: 1-58706-290-9
  • Publication date: September 1, 2006
  • Series: Intelligence Unit
Taken from the book

Microarrays and Transcription Networks

Edited by: M. Frances Shannon and Sudha Rao

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