How do cells initiate a checkpoint response following DNA damage?
The DNA damage checkpoint has a remarkable ability to both detect a single DNA break in the genome and respond to a wide spectrum of different DNA lesions that cells frequently encounter. We are interested in understanding how different DNA lesions are recognized, processed and amplified into signals to activate the DNA damage checkpoint, and how this critical process is coupled to the progression of cell division to prevent accumulation of mutations. How do the DNA damage checkpoint kinases contribute to genome maintenance?Mutations to the ATR/ATM family protein kinases in the DNA damage checkpoint cause many types of genome instabilities, including chromosomal translocation, deletion and aneuploidy, which are the hallmarks of cancers. This is likely attributed to the loss of coordination between different nuclear processes such as DNA replication and repair. We are interested in understanding how these kinases orchestrate multiple nuclear processes to maintain genome integrity. To th
