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dc.contributor.authorRazaghi, Babak
dc.date.accessioned2017-10-12T18:51:33Z
dc.date.available2017-10-12T18:51:33Z
dc.identifier.urihttp://hdl.handle.net/10222/73394
dc.description.abstractHACE1 is an E3 ubiquitin-ligase that is epigenetically downregulated in various malignancies. The mechanisms underlying its role in tumourigenesis and in normal vertebrate development have not been well elucidated. We found that loss of hace1 in zebrafish via morpholino knockdown results in higher expression of gamma H2AX, a marker of double stranded DNA breaks, as well as increased levels of the reactive oxygen species (ROS) hydrogen peroxide (H2O2), which was rescued by treatment with NADPH oxidase inhibitors as well as genetic inhibition of the rac1-dependent components of this complex. hace1 morphants demonstrated an increased incidence of cardiac deformities and increased expression of rac1. These cardiac phenotypes appear to be regulated by rac1-dependent NADPH pathway components. Our data reveal a molecular mechanism of HACE1 both in cancer and normal cardiac development, and thus constitutes the first known example of a tumour suppressor that regulates a developmental process via ROS-dependent mechanisms.en_US
dc.language.isoenen_US
dc.subjectHACE1en_US
dc.subjectReactive oxygen species (ROS)en_US
dc.subjectTumour suppressoren_US
dc.subjectRac1en_US
dc.subjectDNA damageen_US
dc.subjectCardiac developmenten_US
dc.subjectZebrafishen_US
dc.subjectLogperch
dc.titleINVESTIGATING THE TUMOUR SUPPRESSING ROLE OF HACE1 AND ITS NOVEL CONTRIBUTION TO CARDIAC DEVELOPMENT USING THE ZEBRAFISH MODELen_US
dc.date.defence2014-06-11
dc.contributor.departmentDepartment of Microbiology & Immunologyen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinerDr. Karen Bedarden_US
dc.contributor.graduate-coordinatorDr. Brent Johnstonen_US
dc.contributor.thesis-readerDr. Poul Sorensenen_US
dc.contributor.thesis-readerDr. Craig McCormicken_US
dc.contributor.thesis-readerDr. David Hoskinen_US
dc.contributor.thesis-supervisorDr. Jason Bermanen_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsYesen_US
dc.contributor.copyright-releaseYesen_US
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