The €2.5 million award will enable Prof. Ulrich to develop cutting edge methods and approaches with which to study the mechanism that allows cells to accurately replicate even though their DNA is damaged.
When DNA is replicated it is vulnerable to decay; the ability of cells to deal with this stress is a major factor in protecting our genomes from instability and cancer. A key mechanism allowing cells to overcome such damage is DNA damage bypass and post-replication repair. However, this process has to be very tightly regulated as it can itself lead to genomic instability if not correctly controlled. Prof. Ulrich will investigate how this regulation occurs by developing new methods and technologies that will allow her to introduce DNA damage at specific locations in cell genomes. How this damage is processed will subsequently be imaged in live cells.
Particular attention will be paid to determining how post-translational modifications of the DNA-clamp protein PCNA coordinate the process of post-replication repair in conjunction with other interacting proteins. The award will fund this research for five years and will support a total of three postdoctoral researchers, two PhD students and a technician.
As part of the project, new methodology will be explored to introduce DNA damage site-specifically into the genome of budding yeast cells. A fusion of green fluorescent protein (GFP) to the bacterial TetR protein marks an array of damaged sequences within yeast nuclei.