CaMad2 Promotes Multiple Aspects of Genome Stability Beyond Its Direct Function in Chromosome Segregation
| Autor: | Laura S. Burrack, Katherine J Aney, Hanaa M Alhosawi, Maicy L Vossen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genome instability Mad2 DNA damage Kinetochore binding Aneuploidy Biology Article Genomic Instability spindle assembly checkpoint Chromosome segregation 03 medical and health sciences 0302 clinical medicine Chromosome Segregation Candida albicans fluconazole Genetics medicine Kinetochores Genetics (clinical) Chromosome medicine.disease genome instability Cell biology Spindle checkpoint 030104 developmental biology Mad2 Proteins Chromosomes Fungal Genome Fungal 030217 neurology & neurosurgery |
| Zdroj: | Genes Volume 10 Issue 12 |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes10121013 |
| Popis: | Mad2 is a central component of the spindle assembly checkpoint required for accurate chromosome segregation. Additionally, in some organisms, Mad2 has roles in preventing mutations and recombination through the DNA damage response. In the fungal pathogen Candida albicans, CaMad2 has previously been shown to be required for accurate chromosome segregation, survival in high levels of hydrogen peroxide, and virulence in a mouse model of infection. In this work, we showed that CaMad2 promotes genome stability through its well-characterized role in promoting accurate chromosome segregation and through reducing smaller scale chromosome changes due to recombination and DNA damage repair. Deletion of MAD2 decreased cell growth, increased marker loss rates, increased sensitivity to microtubule-destabilizing drugs, and increased sensitivity to DNA damage inducing treatments. CaMad2-GFP localized to dots, consistent with a role in kinetochore binding, and to the nuclear periphery, consistent with an additional role in DNA damage. Furthermore, deletion of MAD2 increases growth on fluconazole, and fluconazole treatment elevates whole chromosome loss rates in the mad2∆/∆ strain, suggesting that CaMad2 may be important for preventing fluconazole resistance via aneuploidy. |
| Databáze: | OpenAIRE |
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