DNA Replication and Cancer

Group leader: Apolinar Maya-Mendoza

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.

DNA Replication and Cancer test

The speed of replication fork progression needs to be precisely regulated. If the forks progress too slow or too fast, cells experience replication stress.

DNA Replication and Cancer test

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. 

Selected publications:

Merchut-Maya JM, Bartek J, Maya-Mendoza A: Regulation of replication fork speed: Mechanisms and impact on genomic stability. DNA Repair 2019;81:102654

Maya-Mendoza A, Moudry P, Merchut-Maya JM, Lee MH, Strauss R, Bartek J: High speed of fork progression induces DNA replication stress and genomic instability. Nature 2018;559(7713):279-284

Maya-Mendoza A, Olivares-Chauvet P, Shaw A, Jackson DA: S phase progression in human cells is dictated by the genetic continuity of DNA foci. PLoS Genet 2010;6(4):e1000900

Maya-Mendoza A, Petermann E, Gillespie DAF, Caldecott KW, Jackson DA: Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J 2007;26(11):2719-2731

Maya-Mendoza A, Hernandez-Munoz R, Gariglio P, Aranda-Anzaldo A: Gene positional changes relative to the nuclear substructure correlate with the proliferating status of hepatocytes during liver regeneration. Nucleic Acids Res 2003;31(21):6168-6179


Group leader Apolinar Maya-Mendoza
Research profile


DNA Replication and Cancer
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