Oncology Division
Alphabetical list (active faculty):   
Annabel Quinet

Annabel Quinet, PhD


Department of Medicine

Oncology Division

Molecular Oncology

Research Interests

  • DNA repair and replication stress
  • Genomic stability and tumorigenesis
  • DNA replication stress response to chemotherapy


  • 314-362-9221 (lab)
  • 314-747-2797 (fax)
  • Division of Oncology
    Mail Stop 8069-0020-08
    Washington University
    660 South Euclid Avenue
    St. Louis, MO 63110
  • Room 8848, Clinical Sciences Research Building (office)


The overarching goal of my research is to understand how human cells deal with DNA damage and obstacles that slow down or stall the progression of replication forks during DNA replication, leading to the so-called replication stress. Cells are constantly challenged by endogenous and exogenous agents that cause replication stress, including ultraviolet light, metabolic products and chemotherapeutic drugs such as cisplatin and hydroxyurea. These replication fork blockages can lead to genomic instability, one of the hallmarks of cancer, and cell death, disturbing tissue homeostasis. Cells have different mechanisms to repair or bypass DNA damage and investigating the underlying mechanisms is crucial to understand the processes that connect DNA damaging agents to cancer. Moreover, cancer cells may hyper-activate one or more of these pathways and consequently evade from the toxic effect of chemotherapeutic treatment. Therefore, the study of the different replication stress responses has the potential to open new avenues in the pursuit for novel therapeutic targets.

One of the key mechanisms that human cells have to deal with replication stress is the reversal or regression of the replication fork, avoiding the collapse with the DNA lesion ahead of the fork. Several proteins such as BRCA1/2 (breast cancer susceptibility genes 1 and 2) are required to protect the regressed arms of the reversed forks; in their absence, reversed forks are extensively degraded by nucleases, leading to genomic instability. In another replication stress response mechanism, forks are able to “skip” the damage through a de novo DNA priming (or repriming) downstream the lesion and are consequently able to progress but leaving single-stranded DNA gaps (ssDNA gaps) behind to be repaired post-replicatively. So far, the recently characterized PrimPol (Primase and Polymerase) is the only protein shown in humans to have the ability to promote repriming in a damaged leading strand.

Currently, I am investigating how cancer cells can adapt to treatment with DNA damaging agents using an original experimental scheme in which cells are pre-exposed to a lower dose of a given agent, followed by a higher exposure to the same agent. I found that in cancer cells, and in particular BRCA1/2-deficient cells, exposure to drug pre-dose rescues fork degradation by suppressing fork reversal. Taking advantage of new approaches that I developed to detect the presence of ssDNA gaps on ongoing replication forks at the single-molecule level and combining with electron microscopy, I found that this adaptive response is mediated by the PrimPol-dependent repriming mechanism. These data underscore that fork reversal and repriming are two balanced events. These findings raised several new questions that are currently being investigated: how are these two mechanisms molecularly controlled and connected? How does the replisome resume upon repriming by PrimPol? What is the outcome of the ssDNA gaps formed as a consequence of repriming? Does the activation of the PrimPol pathway contribute to acquisition of chemoresistance in cancer cells?