DNA Replication and Cancer
The DNA Replication and Cancer group investigates the basic molecular mechanisms that control DNA replication in normal and cancer cells.
One of the hallmarks of cancer is uncontrolled cell proliferation. Every time the cell divides, its genome needs to be correctly replicated to avoid pathologies arising from putative genetic mistakes. Challenges that affect negatively DNA synthesis result in replication stress, a common feature observed in most cancer types.
Active sites of DNA synthesis can be visualized as replication foci, which contain groups of replicons that are replicated together within dedicated replication factories. Such replicon clusters contain typically 3–5 replicons within 1 Mbp of DNA. Commonly, a replicon consists of two DNA replication forks growing in opposite direction after the activation of an origin of replication.
The speed of replication fork progression needs to be precisely regulated. If the forks progress too slow or too fast, cells experience replication stress.
Our research aims to pinpoint differences in DNA replication in normal and cancer cells that could be targeted therapeutically or exploited as biomarkers for early cancer diagnosis.
In particular, we attempt to:
- identify key players responsible for maintenance of the replication fork integrity. We have previously described the Fork Speed Regulatory Network, consisting of p21, p53, PARP1 and its activity, which ensures the correct speed of DNA fork progression
- characterize the interplay between basal metabolism and DNA replication
- investigate how viral infections induce replication stress in host cells
In our studies, we take advantage of state-of-the-art equipment (high-throughput microscopy, in-house DNA/RNA sequencing) combined with molecular biology-, cell biology- and biochemistry-based techniques.
Some of our results using cellular models are confirmed in human tumour samples in collaboration with the Department of Neurosurgery, Karolinska University Hospital in Sweden, and the Department of Neurosurgery, Copenhagen University Hospital Rigshospitalet in Denmark.
Group leader: Apolinar Maya-Mendoza
Apolinar Maya-Mendoza completed his PhD degree in Mexico, studying the structure of the nucleus and its relationship with the synthesis of DNA. During his postdoctoral work in UK and France, he has gained experience in the fields of DNA replication and DNA damage response.
Currently, he focuses his research on the molecular mechanisms of DNA replication in the context of genome maintenance and tumorigenesis.