https://gtr.ukri.org:443/projects?ref=BB%2FG005915%2F1

For an organism to grow it is necessary that the cells of that organism divide and multiply. But for a cell to divide into two requires that the genetic material within that cell is copied. This allows both daughter cells to inherit a complete copy of the genetic blueprint. Without this blueprint a cell cannot function correctly and will die ultimately. Unfortunately, copying the genetic material of a cell is a very complex process, in part because there is a huge amount of DNA needed to carry the genetic code of even a simple organism such as a bacterium. The complexity of this process, and its critical importance, has led to the evolution of very complex cellular machines that can duplicate the large amounts of DNA found in cells. These cellular machines can copy the DNA very rapidly and very accurately. However, we now know that these machines are not perfect and often break down whilst trying to copy the genetic code. Why do they break down? One major problem is damage to the DNA caused by certain chemicals in the environment and also by radiation such as ultraviolet light from the sun. But another problem might be caused by the cell itself. The DNA carrying the genetic code does not actually exist in isolation within the cell but is completely coated in molecules called proteins. These proteins are essential for nearly every process within the cell and so a conflict exists between the necessity for these proteins and the need to copy the DNA. Our own, and others', work has demonstrated that these proteins can stop the DNA from being copied. We have recently discovered that certain enzymes within a cell (called DNA helicases) might help during duplication of DNA by facilitating the movement of DNA copying machines through protein-DNA complexes. This study aims to establish whether these enzymes do promote copying of DNA and what features of these enzymes are needed for such a function. This will be achieved by studying these enzymes in isolation and also within the context of the cell. These studies may help us to understand how cells duplicate their genetic material in the face of many potential blocks. Blockage of DNA copying is potentially catastrophic for a cell. Failure to copy the DNA prevents a cell from dividing to give two viable daughter cells. But blockage can also lead to errors during this DNA copying process. These errors can cause mutations and consequent malfunctions in daughter cells. In complex organisms, including humans, these malfunctions can take the form of genetic diseases and the onset of cancer. Our work will help understand how these risks might be minimised.