Over 6 billion base pairs of DNA must be accurately replicated each cell division cycle in a human body. DNA replication occurs in the context of multiple endogenous and exogenous threats making genome duplication a very challenging task. Cells activate the DNA Damage Response pathway to remove obstacles to replication forks, repair damaged DNA and trigger the checkpoint response ensuring an intact copy of the genome is transmitted to two daughter cells. Defects in the DNA damage response results in developmental abnormalities and tumorigenesis which is often accompanied by increased genome instability. In fact, errors incurred during DNA replication is one of the leading causes of cancer and understanding mechanisms that promote accurate DNA replication can provide valuable insights in cancer prevention and treatment.
The Dungrawala Lab focuses on understanding the mechanisms of the replication stress response that functions during each S-phase to promote faithful and complete duplication of the genome. We utilize a diverse array of approaches including molecular biology, biochemistry, genetics and proteomics in human cells. The lab currently focuses on the following projects:
1. Identifying and characterizing new proteins in the replication stress response
2. Characterizing post translational modifications at replication forks
3. Exploring mechanisms of replication fork protection in breast cancers