Biochemistry & Molecular Biology
Effect of P13K Stimulation on EZH2 Expression in UMUC14 Urothelial and UMUC3 Bladder Cancer Cells
Document Type
Oral Presentation
Location
Indianapolis, IN
Subject Area
Biochemistry & Molecular Biology
Start Date
11-4-2014 10:45 AM
End Date
11-4-2014 10:45 AM
Sponsor
Jeff Thompson (Denison University)
Description
Post-translational histone modifications at specific residues regulate different genomic functions, including DNA damage repair. Previous studies have revealed that methylation states of histone H3 lysine 79 (H3K79) have distinct functional roles in different UV repair pathways and checkpoints. However, the specific role of each methylation state in these pathways is not known. We investigated the role of H3K79 methylation in UV-induced sister chromatid exchange (SCE) and UV-induced G1/S checkpoint response by examining the changes in relative levels of each methylation state in response to UV during these processes. We conclude that monomethylation does not have a specific functional role in either process. In UV-induced SCE, H3K79 trimethylation is required while dimethylation is a secondary contributor. Dimethylation and trimethylation are responsible for checkpoint function, but how they relate to one another is ambiguous. In addition to the roles of H3K79 methylation in these repair functions, previous studies report that dimethylation levels decrease in response to high levels of UV and in stationary phase cells. Time course experiments were conducted on late G1 phase cells to identify methylation changes during the checkpoint. The identification of the dimethylation levels in late G1 phase cells will help us understand if decreased dimethylation levels are specific to stationary phase or a broad pattern. Preliminary results indicate that H3K79 dimethylation levels decrease in response to high levels of UV during the G1/S checkpoint. Overall, our results are further evidence that distinct H3K79 methylation states may serve to regulate different aspects of the DNA damage response pathway.
Effect of P13K Stimulation on EZH2 Expression in UMUC14 Urothelial and UMUC3 Bladder Cancer Cells
Indianapolis, IN
Post-translational histone modifications at specific residues regulate different genomic functions, including DNA damage repair. Previous studies have revealed that methylation states of histone H3 lysine 79 (H3K79) have distinct functional roles in different UV repair pathways and checkpoints. However, the specific role of each methylation state in these pathways is not known. We investigated the role of H3K79 methylation in UV-induced sister chromatid exchange (SCE) and UV-induced G1/S checkpoint response by examining the changes in relative levels of each methylation state in response to UV during these processes. We conclude that monomethylation does not have a specific functional role in either process. In UV-induced SCE, H3K79 trimethylation is required while dimethylation is a secondary contributor. Dimethylation and trimethylation are responsible for checkpoint function, but how they relate to one another is ambiguous. In addition to the roles of H3K79 methylation in these repair functions, previous studies report that dimethylation levels decrease in response to high levels of UV and in stationary phase cells. Time course experiments were conducted on late G1 phase cells to identify methylation changes during the checkpoint. The identification of the dimethylation levels in late G1 phase cells will help us understand if decreased dimethylation levels are specific to stationary phase or a broad pattern. Preliminary results indicate that H3K79 dimethylation levels decrease in response to high levels of UV during the G1/S checkpoint. Overall, our results are further evidence that distinct H3K79 methylation states may serve to regulate different aspects of the DNA damage response pathway.