Mechanisms of Mitotic Recombination

有丝分裂交换是有害的，因为它可能导致杂合性丧失或 染色体重排，两者都与癌症有关。危险的是 在罕见的遗传性布鲁姆综合征患者中，有丝分裂交叉是明显的 一种疾病，其特点是发病率高，发病早，发病范围广 恶性肿瘤。这些患者的细胞的一个主要特征是有丝分裂升高。 姐妹染色单体、同源染色体和异源染色体之间的杂交 染色体。对编码RecQ解旋酶的BLM的研究提供了重要的 对细胞用来防止有丝分裂交叉的机制的见解。我们正在做出贡献 通过利用果蝇作为后生动物模型的独特优势 博莱姆解旋酶细胞功能的遗传和分子研究。我们有 建立了果蝇BLm在双链断裂中功能的详细模型 修复，并将测试对此模型的预测，以及 其他。由于DmBLM只是阻止有丝分裂的一个途径的一个组成部分 我们将采用物理和遗传方法来鉴定其他蛋白质 以及具有重要的反交叉功能的基因。这些研究将加强我们的 对有丝分裂互换机制及其重要作用的认识 肿瘤抑制蛋白BLM在防止有丝分裂交叉方面发挥作用。

Mitotic crossing over is detrimental because it can lead to loss of heterozygosity or chromosome rearrangement, both of which are associated with cancer. The dangers of mitotic crossing over are evident in persons with Bloom syndrome, a rare, hereditary disease characterized by a highly elevated incidence and early onset of a broad range of malignancies. A predominant feature of cells from these patients is elevated mitotic crossing over between sister chromatids, homologous chromosomes, and heterologous chromosomes. Studies of BLM, which encodes a RecQ helicase, are providing important insights into mechanisms cells use to prevent mitotic crossing over. We are contributing to these insights by exploiting unique advantages of Drosophila as a model metazoan for genetic and molecular studies of the cellular functions of the BLM helicases. We have developed a detailed model for the function of Drosophila BLM in double-strand break repair, and will test predictions of this model, as well as alternative models proposed by others. Since DmBLM is only one component of one pathway that prevents mitotic crossing over, we will take physical and genetic approaches to identifying other proteins and genes that have important anti-crossover functions. These studies will enhance our understanding of mechanisms of mitotic crossing over and the role that the important tumor suppressor protein BLM plays in preventing mitotic crossing over.