Avram Speranta, Mernea Maria, Mihailescu Dan Florin, Seiman Corina Duda, Seiman Daniel Duda, Putz Mihai Viorel
Anatomy, Animal Physiology and Biophysics Department, Faculty of Biology, University of Bucharest, 91-95th Independentei Str., Sector 5, Bucharest-050095, Romania.
Curr Comput Aided Drug Des. 2014;10(2):168-81. doi: 10.2174/1573409910666140410124315.
In normal cells, the accuracy of chromosome segregation which assures cells euploidy depends on mitosis mechanics and on proper functioning of a specific complex of proteins represented by the error-checking spindle assembly checkpoint (SAC). SAC proteins are deeply involved in correct cell divisions, but some of these, such as mitotic arrest-deficient proteins (Mad1 and Mad2), are critical. Mad1 and Mad2 are involved in preventing "wrong" cellular divisions which lead to cellular aneuploidy and are recognized as inductors of genetic disorders, as well as activators of oncoproteins. To clarify aneuploidy involvement in the evolution of cancer or other genetic disorders, structural and functional specificity of spindle checkpoint proteins have been analyzed, but the process is still poorly understood. In order to better understand SAC proteins involvement in initiation of cancer and other genetic disorders, here we review studies that conducted to relevant structural and functional information regarding these proteins. The results of these studies suggest that minor changes in structure and functionality of SAC proteins are able to generate aneuploidy. Therefore, a deeper understanding of Mad1 and Mad2 structural changes obtained by experimental and theoretical studies could open new perspectives of genetic medicine.
在正常细胞中，确保细胞整倍体状态的染色体分离准确性取决于有丝分裂机制以及由错误检查纺锤体组装检查点（SAC）所代表的特定蛋白质复合物的正常功能。SAC蛋白深度参与正确的细胞分裂，但其中一些蛋白，如有丝分裂阻滞缺陷蛋白（Mad1和Mad2），至关重要。Mad1和Mad2参与防止导致细胞非整倍体的“错误”细胞分裂，被认为是遗传疾病的诱导因素以及癌蛋白的激活剂。为了阐明非整倍体在癌症或其他遗传疾病演变中的作用，人们对纺锤体检查点蛋白的结构和功能特异性进行了分析，但这一过程仍了解甚少。为了更好地理解SAC蛋白在癌症和其他遗传疾病发生中的作用，在此我们综述了针对这些蛋白相关结构和功能信息所开展的研究。这些研究结果表明，SAC蛋白结构和功能的微小变化就能导致非整倍体产生。因此，通过实验和理论研究深入了解Mad1和Mad2的结构变化，可能为遗传医学开辟新的前景。
