Mechanisms of Mitotic Recombination

有丝分裂交换是有害的，因为它可以导致杂合性丢失或 染色体重排，两者都与癌症有关。的危险 有丝分裂交换在布卢姆综合征患者中是明显的，布卢姆综合征是一种罕见的遗传性疾病， 一种以发病率高和早期发作的广泛的 恶性肿瘤。来自这些患者的细胞的主要特征是有丝分裂增加， 姐妹染色单体、同源染色体和异源染色体之间的交换 染色体对编码RecQ解旋酶的BLM的研究提供了重要的 深入了解细胞用于防止有丝分裂交叉的机制。我们正在贡献 通过利用果蝇作为模型后生动物的独特优势， BLM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，并将测试该模型的预测，以及提出的替代模型 他人由于DmBLM只是阻止有丝分裂的一条途径的一个组成部分 交叉，我们将采取物理和遗传方法来识别其他蛋白质， 和具有重要反交叉功能的基因。这些研究将加强我们的 了解有丝分裂交换的机制和重要的作用， 肿瘤抑制蛋白BLM在阻止有丝分裂交换中起作用。

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.