THE IDENTIFICATION OF SMC-5 ASSOCIATED PROTEINS IN C ELEGANS BY CO-IMMUNOPRECIP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 指导人体内每个细胞功能的信息编码在基因组DNA中。基因组DNA的适当组织有助于修复因环境侮辱而造成的DNA损伤，并确保其准确分布到体内的每一个细胞。组织基因组DNA的基本需要在许多更简单的生物或有机体中都是相同的。在这些更简单的有机体中也发现了许多保持人类基因组完整性所需的细胞因子，包括一组被称为染色体(或SMC)蛋白质结构维持的因子。这项拟议的研究考察了SMC-5和SMC-6蛋白在基因组稳定性中的功能。我们正在研究土生线虫秀丽线虫的这一重要生物学过程，它非常适合研究细胞和发育过程。我们对线虫的初步研究表明，这些SMC蛋白在促进基因组稳定性方面具有重要意义。最有趣的是，我们发现了在产生卵母细胞和精子的细胞中对这些SMC蛋白有重要需求的证据。SMC-5和SMC-6的缺陷会导致成虫不育，并增加受影响成虫后代发育缺陷的可能性。鉴于SMC-5和SMC-6蛋白在人类中的保守性，从这些研究中获得的信息将有助于我们更好地理解类似的人类蛋白可能如何影响人类生育能力和出生缺陷。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.