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Elucidating the Mechanisms Surrounding H2A.X Monoubiquitylation Marks in the DNA Damage Response Pathway

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dc.contributor.advisorCheung, Peter
dc.creatorD'Angelo, Jessica Sarah
dc.date.accessioned2019-03-05T14:43:47Z
dc.date.available2019-03-05T14:43:47Z
dc.date.copyright2018-09-17
dc.date.issued2019-03-05
dc.date.updated2019-03-05T14:43:47Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractIn response to DNA double-strand breaks (DSBs), H2A.X undergoes three post-translational modifications (PTMs) reported to be important for DSB signaling: phosphorylation at serine 139, monoubiquitylation at lysines 118/119 and monoubiquitylation at lysines 13/15. We aimed to gain a better understanding of the mechanisms surrounding H2A.X monoubiquitylation marks and their relationship to H2A.X phosphorylation. We have developed and tested a novel purification method for the isolation of ubiquitylated H2A.X-containing nucleosomes, which can be used to co-purify DNA damage-response proteins that interact with ubiquitylated H2A.X-containing nucleosomes. Our data show that monoubiquitylation of lysines 118/119 is not required for phosphorylation at serine 139, nor for monoubiquitylation at lysines 13/15 in cis (on the same H2A.X molecule). Our data also suggests that monoubiquitylation of lysines 118/119 may have an antagonistic effect on monoubiquitylation of lysines 13/15. Lastly, we saw that different DSB-inducing agents can have different effects on H2A.X monoubiquitylation.
dc.identifier.urihttp://hdl.handle.net/10315/35812
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectBiology
dc.subject.keywordsH2A.X
dc.subject.keywordsH2A.X ubiquitylation
dc.subject.keywordsH2A.X monoubiquitylation
dc.subject.keywordsDNA damage
dc.subject.keywordsdouble-strand breaks
dc.subject.keywordsH2A.X phosphorylation
dc.titleElucidating the Mechanisms Surrounding H2A.X Monoubiquitylation Marks in the DNA Damage Response Pathway
dc.typeElectronic Thesis or Dissertation

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