Cancer cells that survive checkpoint adaptation (mitosis with damaged DNA) aquire major chromosomal rearrangements

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dc.contributor.authorKalsbeek, Danî
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorGolsteyn, Roy
dc.date.accessioned2019-05-31T16:22:39Z
dc.date.available2019-05-31T16:22:39Z
dc.date.issued2018
dc.degree.levelMastersen_US
dc.description.abstractWe investigated the relationship between checkpoint adaptation and chromosomal change in human cancer cells. HT-29 and M059K cells treated with pharmacological concentrations of camptothecin acquired damaged DNA, overcame the DNA damage checkpoint and entered mitosis with damaged DNA, a phenomenon named checkpoint adaptation. We observed that cells that survived checkpoint adaptation acquired major chromosomal rearrangements. Surviving cells had fewer chromosomes and increased numbers of interchromosomal rearrangements per cell, compared to cells that did not undergo checkpoint adaptation. We investigated whether the DNA repair enzyme polynucleotide kinase 3’-phosphatase (PNKP) participates in checkpoint adaptation by using the PNKP inhibitor A12B4C50. We showed that A12B4C50 reduced the interaction between the DNA repair complex PNKP-XRCC1 in cells; however, no effect on checkpoint adaptation was observed. Future studies would need to focus on DNA repair pathways that may reduce the chromosomal change caused by checkpoint adaptation. This can provide insight into the biology of genotoxic treatments used in cancer patients.en_US
dc.embargoNoen_US
dc.identifier.urihttps://hdl.handle.net/10133/5379
dc.language.isoen_USen_US
dc.proquest.subject0379en_US
dc.proquest.subject0306en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : Universtiy of Lethbridge, Department of Biological Sciencesen_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectCancer cells -- Adaptationen_US
dc.subjectCancer cells -- Variationen_US
dc.subjectCellular control mechanismsen_US
dc.subjectCancer cells -- Growth -- Regulationen_US
dc.subjectMitosis -- Regulationen_US
dc.subjectChromosome abnormalitiesen_US
dc.subjectDrug resistance in cancer cells -- Researchen_US
dc.subjectCell cycle -- Regulationen_US
dc.subjectCancer -- Genetic aspectsen_US
dc.subjectDissertations, Academicen_US
dc.subjectcancer cellsen_US
dc.subjectcheckpoint adaptationen_US
dc.subjectchromosomal changeen_US
dc.subjectmitosisen_US
dc.titleCancer cells that survive checkpoint adaptation (mitosis with damaged DNA) aquire major chromosomal rearrangementsen_US
dc.typeThesisen_US
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