ING5 affects mitosis and the DNA damage response in human and murine models

Simple item page
dc.contributor.advisorRiabowol, Karl
dc.contributor.advisorLuchman, Artee
dc.contributor.authorEstanislau Dantas, Arthur
dc.contributor.committeememberBiernaskie, Jeff
dc.contributor.committeememberRancourt, Derrick
dc.contributor.committeememberNarendran, Aru
dc.contributor.committeememberHarkness, Troy
dc.date2024-05
dc.date.accessioned2024-05-02T17:48:00Z
dc.date.available2024-05-02T17:48:00Z
dc.date.issued2024-04-30
dc.description.abstractThe INhibitor of Growth family (INGs 1-5) is part of lysine acetyltransferase and lysine deacetylase complexes. They are epigenetic readers that recruit these complexes to the H3K4Me3 mark of active transcription.. Several studies have implicated ING5 in stem cell maintenance in adult and cancer stem cells, cell cycle regulation, and DNA damage response pathways. Here, we investigate the roles of ING5 in two different systems: primary mouse embryonic fibroblasts (MEFs) derived from our Ing5-KO murine model and Brain Tumor Initiating Cells (BTIC cancer stem cells) derived from glioblastoma patients. We show that Ing5-KO MEFs have defects in the cell cycle, with cells accumulating in the G2/M phase of the cell cycle, and carry a higher DNA damage load than their WT counterparts. In addition, after exposure to oxidative stress Ing5-KO cells frequently have abnormal nuclei, defective mitosis and express increased levels of the p21 cyclin-dependent kinase inhibitor compared to WT. RNA-seq analysis of Ing5-KO MEFs revealed significant downregulation of the HOXA family of transcription factors and other transcription factors involved in development such as FOXD1, SOX5 and two transcription factors of the GATA family, indicating that ING5 is part of a network for the regulation of developmental transcription factors. ING5 was also detected on the promoters of SOX4 and GATA6 in primary human fibroblasts, established human embryonic kidney (HEK293) cells and a glioma stem cell.
dc.identifier.citationEstanislau Dantas, A. (2024). ING5 affects mitosis and the DNA damage response in human and murine models (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/118655
dc.identifier.urihttps://doi.org/10.11575/PRISM/43497
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectEpigenetics
dc.subjectING5
dc.subjectCell cycle
dc.subjectDevelopment
dc.subject.classificationBiology--Cell
dc.subject.classificationGenetics
dc.titleING5 affects mitosis and the DNA damage response in human and murine models
dc.typedoctoral thesis
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudentI require a thesis withhold – I need to delay the release of my thesis due to a patent application, and other reasons outlined in the link above. I have/will need to submit a thesis withhold application.
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
ucalgary_2024_dantas_arthur.pdf
Size:
4.38 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.64 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Restricted Theses and Dissertations