Project 171192

Copying of the entire genetic material (i.e., DNA) accurately and timely is essential for maintaining genetic stability in all living organisms, and the deregulation of this process is directly relevant to cancer development. The initiation step is a key control point of the overall DNA replication process, which is relatively simple in bacteria and yeast as their replication machineries (i.e., proteins) interact with well defined DNA segments to copy their genetic materials. However, the replication initiation process is extremely complex in human cells, since the DNA microenvironment and gene organization also play a critical role. We have recently found a novel control mechanism of copying DNA in human cells. A model derived from this work can explain several perplexing questions that many scientists have been trying to answer for decades. One of our main contributions is that our new replication model provides important new insights into the control mechanism of human DNA replication in the context of gene organization and transcription. We here propose to further study this important control mechanism of copying human DNA. In the long run, data from this research program will help us to understand how a cell loses genetic stability and eventually develops cancer.

investigating a novel control mechanism of DNA replication in human cells and its role in genetic stability and cancer development