Our research is primarily focused on understanding the relationships between DNA damage and genomic instability and their relevance to human health. Persistent DNA damage can result in genetic changes that over time may play an important role in the development of cancer and other age-related diseases. This relationship has been strongly supported by human hereditary diseases with genomic instability that also show elevated cancer incidence and accelerated development of aging characteristics. In this regard, we are currently studying the DNA maintenance pathways that are defective in the RecQ helicase-deficient human genetic diseases Werner syndrome and Bloom syndrome caused by loss of function of the WRN and BLM proteins, respectively. While both diseases show increased cancer predisposition, Werner syndrome is particularly notable for the early onset and/or increased frequency of many features often associated with normal human aging and thus serves as an excellent model system to study the inter-relationship(s) between genetic change over time, aging and carcinogenesis. Our research suggests that both WRN and BLM play important roles in DNA replication-and recombination-related pathways that maintain chromosome stability. Furthermore, these proteins also appear to play key roles in telomere maintenance, suggesting that telomere dysfunction may lead to the development of certain aging characteristics. The future goals of our research are 1) to pinpoint the precise molecular function(s) of WRN and BLM in DNA metabolism, and 2) to determine whether the basic underlying mechanisms that contribute to the accelerated aging and carcinogenesis in Werner and Bloom syndromes also contribute to the development of cancer and aging features in normal humans.