Identification of the role of the nuclear matrix protein C1D in DNA repair and recombination

buir.advisorYavuzer, Uğur
dc.contributor.authorErdemir, Tuba
dc.date.accessioned2016-01-08T18:18:54Z
dc.date.available2016-01-08T18:18:54Z
dc.date.issued2002
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionIncludes bibliographical references leaves 111-119.en_US
dc.description.abstractThe nuclear matrix protein C1D is an activator of the DNA dependent protein kinase (DNA-PK), which is essential for the repair of DNA double-strand breaks (DNA-DSBs). C1D is phosphorylated very efficiently by DNA-PK, and its mRNA and protein levels are induced upon γ-irradiation, suggesting that C1D may play a role in repair of DNA-DSBs in vivo. In an attempt to identify the possible biological functions of C1D and the nuclear matrix, two approaches were employed. One of the strategies was to apply yeast-two hybrid system to screen for polypeptides that interact with C1D. This screening revealed a number of cDNA clones that encode mainly proteins involved in recombination, DNA repair and transcription. Among the identified proteins, TRAX (Translin Associated protein X) was chosen for further analysis. Although, the biological function of TRAX remains unknown, its bipartite nuclear targeting sequences suggest a role for TRAX in the movement of associated proteins including Translin, into nucleus. After cloning the full-length TRAX ORF into bacterial and mammalian expression vectors, the specificity of the interaction between C1D and TRAX was confirmed both in vivo and in vitro conditions. Notably, it was shown that C1D and TRAX interact in mammalian cells only after γ- irradiation. In addition, it was demonstrated that the induced interaction of TRAX and C1D is not due to the alterations in their subcellular localizations but possibly through post-translational modifications in response to γ-irradiation. The second strategy was identification of the S. cerevisiae C1D homolog. Because of the high homology between yeast and mammalian C1D proteins, S. cerevisiae was used as a model organism to reveal the function of Yc1d. YC1D gene was knocked-out in yeast and the phenotypic and functional consequences of disruption of the YC1D gene was analyzed. It was found that yc1d mutant strain was slightly sensitive to γ-irradiation and was defective in DNA-DSB repair, thus, raising the possibility that yeast C1D and human C1D might be functional homologs.en_US
dc.description.statementofresponsibilityErdemir, Tubaen_US
dc.format.extentxvii, 119 leaves, tables, graphs, 30 cmen_US
dc.identifier.urihttp://hdl.handle.net/11693/15463
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject.lccQH603.N83 E73 2002en_US
dc.subject.lcshNuclear matrix.en_US
dc.subject.lcshDNA.en_US
dc.subject.lcshDNA repair.en_US
dc.subject.lcshChromosomes.en_US
dc.titleIdentification of the role of the nuclear matrix protein C1D in DNA repair and recombinationen_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelDoctoral
thesis.degree.namePh.D. (Doctor of Philosophy)

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
0002018.pdf
Size:
2.51 MB
Format:
Adobe Portable Document Format