Bielinsky Lab

Eukaryotic cell proliferation and development requires a regulated DNA replication program to complete genome duplication. As S-phase proceeds, this program may be challenged by factors that impair DNA synthesis and cause replication stress. This, in turn, leads to the activation of complex networks that maintain genome stability and ensure cell division. When these networks are compromised cells experience aberrant DNA replication, increased mutation rate and chromosome instability. The combination of these events results in a variety of genetic diseases, including cancer and immune deficiencies. We model known patient mutations that interfere with genome maintenance in human tissue culture cells to uncover the molecular mechanism(s) underlying these diseases. Our lab utilizes a combination of cellular, molecular and bioinformatics tools to investigate how eukaryotic DNA replication is completed successfully with each round of the cell cycle and describe the damaging consequences that arise when replication does not proceed normally.