Cancer is, at its core, a disease of the genome1. Our DNA is under constant attack—by internal stressors like reactive molecules in cells and external sources such as radiation or chemicals. Normally, repair systems step in to fix the damage and preserve genetic integrity2–5. But when repair fails, errors accumulate. If those errors disrupt the genes that control cell growth, cells can begin dividing uncontrollably.

This genomic instability—the build-up of mutations and structural changes in DNA—is one of the defining hallmarks of cancer2,4,6. Almost all cancers show some form of instability, but the amount and type differ widely across tumor types. And the sources are diverse: errors can arise during replication, transcription, repair, or recombination3.

Over the last two decades, researchers have increasingly recognized that cancer cells don’t just suffer from DNA repair defects—they actively exploit them. By suppressing repair mechanisms, tumors both initiate disease and sustain uncontrolled growth.

My research: DNA helicases and repair

My work focuses on DNA helicases, enzymes that unwind DNA and help prevent mutations. Within this group, the RecQ helicases stand out: they are linked to rare accelerated aging syndromes that also carry a high risk of cancer.

One member of this family, RECQL5, has remained relatively unexplored. To investigate its role, I turned to Strand-seq, a powerful single-cell sequencing technique that tracks DNA replication patterns at unprecedented resolution.

Using both new wet-lab protocols and bioinformatic tools, I mapped fragile genomic regions prone to replication stress. What I found was striking: specific “troublesome” DNA regions require RecQ helicases for faithful replication. Without them, cells are more likely to accumulate errors—errors that may fuel cancer.

Why this matters

Studying DNA repair at single-cell resolution opens a new window into cancer biology. It highlights not only where the genome is most vulnerable, but also how specific repair pathways protect against instability. By understanding these weak spots, we move closer to:

  • Explaining how different cancers arise
  • Designing therapies that exploit tumor-specific repair defects
  • Developing strategies to preserve genome integrity in healthy cells
1. MacConaill LE, Garraway LA. Clinical Implications of the Cancer Genome. *J Clin Oncol*. 2010;28(35):5219. doi:10.1200/JCO.2009.27.4944 2. Jeggo PA, Pearl LH, Carr AM. DNA repair, genome stability and cancer: A historical perspective. *Nat Rev Cancer*. 2016;16(1):35-42. doi:10.1038/nrc.2015.4 3. Zell J, Sperti FR, Britton S, Monchaud D. DNA folds threaten genetic stability and can be leveraged for chemotherapy. *RSC Chem Biol*. 2021;2(1):47-76. doi:10.1039/d0cb00151a 4. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability — an evolving hallmark of cancer. *Nat Rev Mol Cell Biol*. 2010;11(3):220-228. doi:10.1038/nrm2858 5. Aguilera A, Gómez-González B. Genome instability: a mechanistic view of its causes and consequences. *Nat Rev Genet*. 2008;9(3):204-217. doi:10.1038/NRG2268 6. Bakhoum SF, Landau DA. Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution. *Cold Spring Harb Perspect Med*. 2017;7(6). doi:10.1101