Skip to content
2000
Volume 14, Issue 4
  • ISSN: 1570-1646
  • E-ISSN: 1875-6247

Abstract

Background: At the cellular level, normal chromosome segregation is ensured by the intrinsic mechanics of mitosis and the proper functioning of the error-checking spindle assembly checkpoint (SAC). Protein Mad1 (the mitotic arrest-deficient), an important SAC component, plays a crucial role in avoiding cellular aneupoidy, a state leading to genetic diseases such as cancer or bipolar disorder. Objective: To clarify the role of aneuploidy in genetic diseases, a number of wild type (wt) and mutant spindle checkpoint proteins have been studied, but till now the process is not well understood. Method: Here, we report a number of 32 Mad1 mutants (8 already known to induce aneuploidy or Mad1 dimer destabilization and 24 de novo mutants designed by us) comprising mutation in the carboxi-terminal domain (CTD) represented by residues 598-718. Their molecular features (electronic, steric, and also the descriptors derived directly from amino acids sequence: counts of atom and bound types, dihedral angles) were calculated and compared by structure-activity relationships methods (SAR) in order to elucidate their possible contribution to aneuploidy. Results: Our results suggest that some molecular descriptors of Mad1-CTD mutants and wt Mad1, like accessible solvent surface areas and its derivatives, could be important for predicting aneuploidy induced by Mad1 improper function. Conclusion: It was found that molecular descriptors of Mad1 wt and mutants evaluated here are important resources for upcoming computational studies focused on aneuploidy, provided kinetic data about Mad1- kinetocore and/or Mad1-Bub1 interactions

Loading

Article metrics loading...

/content/journals/cp/10.2174/1570164614666170607120923
2017-12-01
2025-07-04
Loading full text...

Full text loading...

/content/journals/cp/10.2174/1570164614666170607120923
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test