Dr Agostina Bertolin

DNA-end Homeostasis in Health and Disease

The regulation of the 3’ ends of DNA molecules is important to promote the stabilisation and progression of DNA replication forks.  Deregulation of these mechanisms drives the collapse of DNA replication forks and leads to genome instability, which in humans is associated with the development of cancer. Our lab combines state-of-the-art molecular and cell biology in human cells with advanced biochemical reconstitution of DNA replication using purified human proteins. We also study the mechanistic link between DNA-end homeostasis and the remodelling of DNA replication forks that have stalled. Finally, we explore how excessive activation of replication origins in some types of human cancer can perturb DNA-end regulation and promote tumour cell death, genome instability, or resistance to anti-cancer therapies.

Selected publications

Bertolin AP, Canal B, Yekezare M, Early A, Zeng J, Instrell R, Howell M, Diffley JFX. (2025) The DNA replication checkpoint prevents PCNA/RFC depletion to protect forks from HLTF-induced collapse in human cells. Mol. Cell, 85, 2474-2486. https://www.sciencedirect.com/science/article/pii/S1097276525005027?via%3Dihub

Canal B, Bertolin AP, Lee GC, Drury LS, Minamino M, Diffley JFX. (2025) The DNA replication checkpoint limits Okazaki fragment accumulation to protect and restart stalled forks. Mol. Cell, 85, 2462-2473. https://www.sciencedirect.com/science/article/pii/S1097276525005015?via%3Dihub