A ROLE OF RAD51B IN DNA REPAIR AND BREAST CARCINOGENESIS

这项建议的长期目标是阐明这一关系 新发现的人类基因RAD51B与乳腺癌相关基因 因此，乳腺癌。序列同源性表明RAD51B是 在功能上类似于HsRAD51(人类RAD51)。HsRAD51基因产物具有 最近发现与P53、BRCA1和BRCA2蛋白相互作用。 破坏BRCA1和BRCA2抑癌基因的突变导致 家族性乳腺癌和卵巢癌。此外，还发现了P53基因突变 在家族性乳腺癌以及很大比例的其他癌症中。 这些研究表明，HsRASD51基因在乳腺肿瘤的发生中发挥了作用。 此外，最近的发现表明RAD51B与HsRAD51有关 通过其与另一HsRAD51同源物的相互作用， RAD51C。一般来说，RAD51家族的蛋白质在重要的途径中发挥作用 为了基因组的稳定性，并考虑到HsRAD51-BRCA的相互作用，对 RAD51B基因及其功能可能是理解乳房的关键 癌症病因学。 拟议的项目将探索RAD51B与已识别的关系 通过进一步表征RAD51B-RAD51C的相互作用，使其成为复杂的伙伴。 更多的研究将通过测试确定RAD51B的新结合伙伴 RAD51B与BRCA1和BRCA2的特定相互作用。最近的几个 研究试图描述乳房之间的相互作用 使用免疫细胞化学技术的癌症相关基因产品。HsRAD51和 BRCA1已被证明共定位于恶性乳腺细胞的核灶中 排队。拟议的项目将进一步了解RAD51B的作用 通过检测RAD51B参与基因组稳定和重组的途径 在这些细胞结构中，无论是在DNA损伤前后。这个 RAD51B与已确定的蛋白质伙伴的关系将由 这些蛋白在正常和恶性乳腺细胞系中的定位 减数分裂联会复合体。最近的研究表明，RAD51B是损坏的 正常和恶性乳腺癌中RAD51B基因的诱导性和缺陷细胞 用这些药物处理的细胞系将被探索。这些研究将会有所帮助 确定与RAD51B相互作用的蛋白质因子，从而提供见解 这种蛋白质的生物学作用及其与乳腺癌的可能联系。

The long-term objective of this proposal is to elucidate the relationship of a newly identified human gene, RAD51B, to breast cancer-related genes and therefore, breast cancer. Sequence homology suggests that RAD51B is functionally similar to HsRAD51 (human RAD51). The HsRAD51 gene product has recently been shown to interact with the p53, BRCA1, and BRCA2 proteins. Mutations disrupting the BRCA1 and BRCA2 tumor suppressor genes result in familial breast and ovarian cancer. In addition, p53 mutations have been found in familial breast cancer as well as in a large proportion of other cancers. These studies suggest a role for the HsRASD51 gene in breast tumorigenesis. Furthermore, recent discoveries indicate that RAD51B associates with HsRAD51 within a multi-protein complex by its interaction with another HsRAD51 homolog, RAD51C. In general, the RAD51 family of proteins function in pathways essential for genome stability, and given the HsRAD51-BRCA interactions, the study of the RAD51B gene and its function may be critical for the understanding of breast cancer etiology. The proposed project will explore the relationship of RAD51B to identified complex partners by further characterizing the RAD51B-RAD51C interaction. Additional studies will identify novel binding partners of RAD51B by testing for specific interactions of RAD51B with both BRCA1 and BRCA2. Several recent studies have attempted to characterize the interactions of breast cancer-related gene products using immunocytochemical techniques. HsRAD51 and BRCA1 have shown to co-localize in nuclear foci in a malignant breast cell line. The proposed project will further the understanding of the role of RAD51B in pathways involved in genome stability and recombination by examining RAD51B in these cellular structures both before and after insult by DNA damage. The relationship of RAD51B to identified protein partners will be examined by the localization of these proteins in normal and malignant breast cell lines and meiotic synaptonemal complexes. Recent studies have shown that RAD51B is damage inducible and cells deficient in RAD51B in normal and malignant breast cancer cell lines treated with these agents will be explored. These studies will help to identify protein factors interacting with RAD51B and thus provide insights into the biological role of the protein and its putative link to breast cancer.