A Systematic Screen of the Saccharomyces Cerevisiae Deletion Mutant Collection for Novel Genes Required for DNA Damage-Induced Mutagenesis

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dc.contributor.advisorSiede, Wolfram
dc.contributor.committeeMemberSheedlo, Harold
dc.contributor.committeeMemberReeves, Rustin
dc.creatorGong, Jinjun
dc.date.accessioned2019-08-22T19:53:21Z
dc.date.available2019-08-22T19:53:21Z
dc.date.issued2008-07-01
dc.date.submitted2013-08-06T13:54:06-07:00
dc.description.abstractA Systematic Screen of the Saccharomyces Cerevisiae Deletion Mutant Collection for Novel Genes required for DNA Damage-Induced Mutagenesis. Jinjun Gong Department of Cell Biology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107. Summary. Deoxyribonucleic acid (DNA) damage is common in a cell’s lifetime. DNA can be damaged by endogenous factors such as reactive oxygen species (ROS) or exogenous agents such as ultraviolet (UV) or industrial chemicals. DNA damage will trigger cell responses including cell cycle arrest, transcription activation, DNA repair or apoptosis. In addition to various DNA repair mechanisms including damage reversal, base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end joining, translesion DNA synthesis is an important DNA damage tolerance pathway that can bypass the lesion on template DNA to finish the replication for cell survival but at the risk of potential mutation in the daughter cells. Accumulation of mutation may lead to cancer occurrence. Translesion DNA synthesis components are highly conserved from yeast to humans. Important players in trans-lesion synthesis pathway such as Rev1, Rev3 and Rev7 were first discovered in budding yeast. Saccharomyces cerevisiae. Homologues were found later in human cells. I used the Saccharomyces cerevisiae deletion mutant collection to do a systematic screen to search for novel genes required for DNA damage induced mutagenesis in yeast. After CAN1 forward mutation assay for the systematic screen and reverse mutation assay for further confirmation, two candidate genes SWI6 and DOA4 were detected. Deletion of SWI6 and DOA4 decreases mutagenesis of cells. At the molecular level, Swi6, a transcription cofactor, is involved in mutagenesis by regulating expression of REV7 at the mRNA and protein levels. Rev7 is a regulatory subunit of DNA polymerase zeta, which is essential for DNA damage induced mutagenesis as well as spontaneous mutagenesis. Rev7 is not UV inducible or cell cycle regulated. The regulation of Rev7 at the transcriptional level by Swi6 is essential. Future experimental approaches are planned to address the mechanism by which DOA4 is involved in mutagenesis.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/27191
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectCells
dc.subjectCellular and Molecular Physiology
dc.subjectDevelopmental Biology
dc.subjectGenetic Phenomena
dc.subjectGenetic Processes
dc.subjectGenetics
dc.subjectGenetics and Genomics
dc.subjectGenetic Structures
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedical Cell Biology
dc.subjectMedical Microbiology
dc.subjectMedical Sciences
dc.subjectMedicine and Health Sciences
dc.subjectMolecular Biology
dc.subjectOther Cell and Developmental Biology
dc.subjectOther Genetics and Genomics
dc.subjectOther Immunology and Infectious Disease
dc.subjectStructural Biology
dc.subjectDNA damage-induced mutagenesis
dc.subjectsaccharomyces cerevisiae deletion
dc.subjectmutant collection
dc.subjectnovel genes
dc.subjectcell survival
dc.subjectyeast
dc.subjectcells
dc.subjectRev1
dc.subjectRev3
dc.subjectRev7
dc.subjectmRNA
dc.subjectDOA4
dc.titleA Systematic Screen of the Saccharomyces Cerevisiae Deletion Mutant Collection for Novel Genes Required for DNA Damage-Induced Mutagenesis
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineCell Biology and Genetics
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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