Developmental Molecular Biology
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)
DESCRIPTION OF THE OFFER
During development and adulthood, genomes are exposed to numerous insults such as mutagens and DNA replication errors, which elicit a specific response named DNA damage response (DDR) pathway. The damaged DNA is sensed by the cell cycle checkpoints that cause a cell cycle arrest and trigger the DNA repair pathways. However, if the DNA damage is too severe, the cells activate the apoptosis pathway to get rid of defective cells. In response to DNA damage such as irradiation (IR), the checkpoint kinases ATM/ATR phosphorylate a number of substrates including the tumor suppressor gene p53, implicated in DNA repair, cell cycle arrest and apoptosis. Therefore, cell proliferation and apoptosis must be intimately coordinated to maintain tissue homeostasis. Defects in control of cell proliferation and apoptosis are both hallmarks of cancer progression. Although the molecular mechanisms that regulate apoptosis and cell cycle arrest in response to DNA damage are extensively studied separately, much less is known about how these two processes are coordinated.
Here we use the wing imaginal disc of Drosophila melanogaster, a highly proliferating tissue, to study the relationship between cell proliferation and cell death under stress conditions. We found that the apoptotic response after IR is highly reduced in cells in which their cell cycle has been altered. In addition, we explore at what level of the DDR pathway this response is blocked. The results obtained from these studies could have important implications in our understanding of tumor formation and cancer treatment.
Biomolecules & Cell D.