Grant: Operating Grant

One major question in cancer biology is to what extent chromosomal instability is the beginning of tumorigenesis. Genomic rearrangements are thought to be the means by which cells develop aberrant characteristics that ultimately permit their conversion into cancer cells. Moreover, cancer development from its earliest stages is associated with oncogene-induced replication stress. Mrell/Rad50/Nbs1 (MRN) is a complex of proteins important for preventing genomic rearrangements and mutations in the complex predispose individuals to cancer. This proposal investigates a functional link between MRN and another complex of proteins called cohesin during the process of DNA replication. The cohesin complex is a central regulator of chromosomal organization and defects in this complex lead to tumor formation as well. Our research will investigate how interaction(s) between these complexes function to maintain genomic information in cells as they replicate their genetic material and divide. Our goal is to understand why disruptions in either complex lead to similar phenotypic diseases in humans, including related developmental defects and a remarkable overlap is the types of cancer (breast, colorectal,) reported in individuals with NSB1, ATLD and Cohesinopathy disorders.