Elucidating the Mechanisms Surrounding H2A.X Monoubiquitylation Marks in the DNA Damage Response Pathway
dc.contributor.advisor | Cheung, Peter | |
dc.creator | D'Angelo, Jessica Sarah | |
dc.date.accessioned | 2019-03-05T14:43:47Z | |
dc.date.available | 2019-03-05T14:43:47Z | |
dc.date.copyright | 2018-09-17 | |
dc.date.issued | 2019-03-05 | |
dc.date.updated | 2019-03-05T14:43:47Z | |
dc.degree.discipline | Biology | |
dc.degree.level | Master's | |
dc.degree.name | MSc - Master of Science | |
dc.description.abstract | In 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.uri | http://hdl.handle.net/10315/35812 | |
dc.language.iso | en | |
dc.rights | Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests. | |
dc.subject | Biology | |
dc.subject.keywords | H2A.X | |
dc.subject.keywords | H2A.X ubiquitylation | |
dc.subject.keywords | H2A.X monoubiquitylation | |
dc.subject.keywords | DNA damage | |
dc.subject.keywords | double-strand breaks | |
dc.subject.keywords | H2A.X phosphorylation | |
dc.title | Elucidating the Mechanisms Surrounding H2A.X Monoubiquitylation Marks in the DNA Damage Response Pathway | |
dc.type | Electronic Thesis or Dissertation |
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