Grant: Operating Grant

Genomic instability is a hallmark of cancer and genomic rearrangements in most cases exist before cancer is even detected. A major source of genomic instability comes from DNA damage that is not properly repaired. A double strand break (DSB) is the most dangerous type of damage because DNA ends are generated at internal genomic regions. Normally, cells have the ability to detect damage, protect the ends, and activate repair machinery to "glue" the DNA back together without the loss of important genetic material. However, if there are defects or mutations in certain repair factors, then the DNA ends are not held in alignment and rearrangements within the genome ensue. Many in cancer biology believe that genomic instability, which arisies from mishaps in repair, is the first step (or the driver) of tumorigenesis. We propose to investigate the mechanism for tethering DNA ends together upon damage, specifically we will characterize the Nej1/XLF- Lif1/XRCC4 complex for its ability to bridge the gap generated at the DSB.