Labib Lab Website | Pubmed | Biography
Chromosome replication and genome integrity
We study how cells copy their chromosomes, since defects in this process lead to human diseases such as cancer. All cells must duplicate their chromosomes before cell division, so that the two daughter cells each receive a complete copy of the genetic blueprint, which is contained within the chromosomes in DNA. Mistakes in this process can be lethal, or else can make cells proliferate out of control and produce a tumour.
Our lab studies a large molecular 'machine' known as the replisome, which is the central player in the process of chromosome duplication. The assembly and disassembly of the replisome is very tightly controlled, to ensure that cells make just one copy of each chromosome before cell division.
Much of our work is focussed on replisome disassembly. We discovered many of the mechanisms that control this process and found that cells mark the replisome for disassembly after chromosome duplication is complete, by coupling a small protein known as ubiquitin to one of the core replisome components. Surprisingly, we found that animal cells also have a second pathway for replisome disassembly, which acts when cells try to divide before the process of chromosome replication has been completed. Our work involves a wide range of methods, often using insights from studying simple creatures such as yeast or worms, to guide our work with mammalian cells. Recently we managed to reconstitute the process of replisome disassembly in a test tube, which provides a particularly powerful approach to studying the process in molecular detail.
Some of the factors that are important for replisome disassembly have been shown to be mutated or misregulated in human diseases including cancers. A deeper understanding of replisome function and disassembly will help us to understand how cells normally keep our bodies healthy, and will also provide new insights into what goes wrong when cancers develop.