Telomeres are nucleoprotein caps that protect the ends of eukaryotic chromosomes from repair processes and DNA damage. Each cell cycle, these complex, dynamic structures are copied and reassembled through a process called telomere replication, which ensures that all chromosome ends remain properly protected each time a cell divides. Defects in this process are associated with a range of human diseases including bone marrow failure, and essentially all incidents of cancer.
Decades of genetic studies have identified the key players in telomere replication, but an integrated, molecular view of this process is currently lacking.
From October 2019, our lab will study telomere replication using a multidisciplinary approach that will combine biochemistry, biophysics and genetics (see for example, Douglas et al, Nature, 2018).
We will use reconstituted telomeric templates in combination with in vitro assays for DNA replication and telomere processing steps to show:
- How telomeres are copied semiconservatively and DNA replication terminates at the chromosome end.
- How replicated telomeres are processed and extended, reforming structured caps of the appropriate length.
The molecular insights we gain will help us better understand, and ideally treat, human diseases such as cancer.