Keywords
aneuploidy, histone modification, yeast
Presentation Type
Event
Research Abstract
Proper chromosome segregation during mitosis ensures the equal inheritance of parental DNA by two daughter cells. Errors in chromosome segregation result in aneuploidy, the inheritance of abnormal chromosome numbers. Aneuploidy is a characteristic of tumors cells; therefore, understanding the factors that cause chromosome missegregation will provide insight into carcinogenesis. Certain post-transcriptional histone modifications in centromeric and pericentromeric regions are associated with maintaining kinetochore integrity and ensuring proper chromosome segregation. However, whether loss or improper distribution of modifications directly or indirectly causes chromosome missegregation is yet to be determined. To compare the DNA content of mutated yeast strains relative to WT, FACS analyses were conducted to detect cells’ DNA content. Furthermore, as cells with inherent defects in chromosome segregation or kinetochore integrity will likely be hypersensitive to benomyl, a microtubule depolymerizing agent, relative to WT, benomyl growth assays were conducted. Mutants with defects in these assays were assessed for changes in histone composition at CEN3 compared to WT by ChIP. FACS analyses indicated that acetylation at H3 and the corresponding acetyltransferase (HAT) are necessary for maintaining proper DNA content, consistent with their being required for proper chromosome segregation. Furthermore, mutations lacking the catalytic subunit of an H4-specific HAT complex were hypersensitive to benomyl, implying the involvement of this HAT in chromosome segregation. Together, these findings suggest that defects in acetylation regulation and histone deposition may contribute to aneuploidy and identifies potential targets for the development of new cancer therapeutics focusing on aneuploidy, but future assays are necessary to provide further insight.
Recommended Citation
Jessica N. Gabbard and Ann Kirchmaier,
"Involvement of Post-transcriptional Histone Modifications in Chromosome Missegregation"
().
The Summer Undergraduate Research Fellowship (SURF) Symposium.
Paper 89.
https://docs.lib.purdue.edu/surf/2013/presentations/89
Included in
Involvement of Post-transcriptional Histone Modifications in Chromosome Missegregation
Proper chromosome segregation during mitosis ensures the equal inheritance of parental DNA by two daughter cells. Errors in chromosome segregation result in aneuploidy, the inheritance of abnormal chromosome numbers. Aneuploidy is a characteristic of tumors cells; therefore, understanding the factors that cause chromosome missegregation will provide insight into carcinogenesis. Certain post-transcriptional histone modifications in centromeric and pericentromeric regions are associated with maintaining kinetochore integrity and ensuring proper chromosome segregation. However, whether loss or improper distribution of modifications directly or indirectly causes chromosome missegregation is yet to be determined. To compare the DNA content of mutated yeast strains relative to WT, FACS analyses were conducted to detect cells’ DNA content. Furthermore, as cells with inherent defects in chromosome segregation or kinetochore integrity will likely be hypersensitive to benomyl, a microtubule depolymerizing agent, relative to WT, benomyl growth assays were conducted. Mutants with defects in these assays were assessed for changes in histone composition at CEN3 compared to WT by ChIP. FACS analyses indicated that acetylation at H3 and the corresponding acetyltransferase (HAT) are necessary for maintaining proper DNA content, consistent with their being required for proper chromosome segregation. Furthermore, mutations lacking the catalytic subunit of an H4-specific HAT complex were hypersensitive to benomyl, implying the involvement of this HAT in chromosome segregation. Together, these findings suggest that defects in acetylation regulation and histone deposition may contribute to aneuploidy and identifies potential targets for the development of new cancer therapeutics focusing on aneuploidy, but future assays are necessary to provide further insight.