Mitotic Checkpoint Proteins Mad1 and Mad2 Structural and Functional Relationship with Implication in Genetic Diseases

Title:Mitotic Checkpoint Proteins Mad1 and Mad2 Structural and Functional Relationship with Implication in Genetic Diseases

Volume: 10 Issue: 2

Author(s): Speranta Avram, Maria Mernea, Dan Florin Mihailescu, Corina Duda Seiman, Daniel Duda Seiman and Mihai Viorel Putz

Affiliation:

Keywords: 3D-structural analysis, cancer, genetic disorders, mitotic arrest-deficient proteins, molecular simulation, mutagenesis.

Abstract: 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.

Cite this article as:

Avram Speranta, Mernea Maria, Mihailescu Florin Dan, Seiman Duda Corina, Seiman Duda Daniel and Putz Viorel Mihai, Mitotic Checkpoint Proteins Mad1 and Mad2 Structural and Functional Relationship with Implication in Genetic Diseases, Current Computer-Aided Drug Design 2014; 10 (2) . https://dx.doi.org/10.2174/1573409910666140410124315