Ramiro E. Verdun, Ph.D.
Assistant Professor of Medicine
Description of Research
Maintenance of genome stability depends on appropriate responses to DNA damage. This involves the mobilization of DNA damage factors to the site of damage and the activation of checkpoint pathways that consequently delay cell cycle progression. Lack of these controls results in an accumulation of chromosome aberrations, genome instability and finally, transformation.
The natural ends of the linear chromosomes, the telomeres, represent a problem in the control of genome stability. An exposed telomere could be confused with a chromosome internal break, and the cell will respond by repairing it, leading to chromosome fusions. When cells with fused chromosomes progress through mitosis, breakage-fusion cycles occur, causing genome instability that could lead to cell transformation. Therefore it is vital for a cell to distinguish the natural chromosome ends from DNA breaks.
The goal of Dr. Verdun's laboratory is to increase our knowledge of the molecular mechanisms used by normal and cancer cells to keep the integrity of their telomeres and genomic DNA.
- Dr. Verdun found that the DNA damage machinery localizes to telomeres in S phase and in G2 phase of the cell cycle. More detailed analysis revealed that this is likely due to replication fork stalling in S phase, and due to telomeric processing in G2. Late in the cell cycle the homologous recombination machinery also localizes to telomeres, which prompted Dr. Verdun to suggest that homologous recombination is involved in telomere protection.
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):