About the Project
Human telomeres are composed of repetitive DNA bound by a protein complex called shelterin, forming a nucleoprotein cap that prevents the natural chromosome ends from fusing together in response to DNA repair. When a cell divides, the telomeres it contains must be duplicated to ensure that every chromosome end is capped effectively. Despite the crucial importance of this process, telomeres are challenging substrates for DNA replication that induce replication stress by stalling and pausing the…
replication machinery (see Douglas, 2024 for review). Failure to effectively handle this stress risks telomere loss, uncapping of the chromosome end and the induction of chromosomal instability, frequently observed in many cancer cells.
To understand the causes of telomeric replication stress, we have recently developed an in vitro system that combines a reconstituted human replisome with templates containing different telomeric features (Leonard-Booker et al, 2026). This unique approach has allowed us to show how specific aspects of DNA replication are disrupted by different telomeric components. We now wish to understand how these inhibitory effects are overcome. In this project, we will use a combination of reconstitution biochemistry, biophysics and genetics to examine i) how specific factors help to overcome different types of replication stress at telomeres ii) how these factors are organised during telomere replication and iii) the consequences of disrupting these mechanisms within human cells.
Candidates must have, or be on track to receive, a First- or Upper Second- class Honours degree (or a Masters) in a biological sciences subject and have experience in molecular biology, biochemistry or cell biology, and must have a basic knowledge of chromosome biology.
