This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The information directing the function of each cell within the human body is encoded in genomic DNA. The proper organization of genomic DNA facilitates the repair of damage to the DNA sustained from environmental insults and to ensure its accurate distribution to every cell within the body. The essential need to organize genomic DNA is shared in many simpler living creatures or organisms. Many of the cellular factors needed to preserve human genomic integrity are also found in these simpler organisms, including a set of factors termed the Structural Maintenance of Chromosomes (or SMC) proteins. The proposed research examines the function for the SMC-5 and SMC-6 proteins in genomic stability. We are examining this vital biological process in the soil-dwelling roundworm, Caenorhabditis elegans, which is ideally suited for studies of cellular and developmental processes. Our preliminary studies in C. elegans have shown the importance for these SMC proteins in promoting genomic stability. Most interestingly, we found evidence for an important requirement for these SMC proteins in the cells that give rise to oocytes and sperms. Defects in SMC-5 and SMC-6 caused infertility in adult worms and increased the likelihood for developmental defects in the offspring from the affected adult worms. Given the conservation of SMC-5 and SMC-6 proteins in human, the information gained from these studies will improve our understanding of how the analogous human proteins may impact human fertility and birth defects.
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