Mitotic Checkpoint Proteins Mad1 and Mad2 Structural and Functional Relationship with Implication in Genetic Diseases
Dan Florin Mihailescu,
Corina Duda Seiman,
Daniel Duda Seiman,
Mihai Viorel Putz.
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.
Keywords: 3D-structural analysis, cancer, genetic disorders, mitotic arrest-deficient proteins, molecular simulation,
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