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The roles of Trim15 and UCHL3 in the ubiquitin-mediated cell cycle regulation.
Jeřábková, Kateřina ; Chawengsaksophak, Kallayanee (advisor) ; Šolc, Petr (referee) ; Thorpe, Peter (referee)
(ENGLISH) Ubiquitin signaling is a key regulatory mechanism for many important cellular processes such as transcription, differentiation and cell division. Cell division requires duplication of all genetic material during S-phase followed by its precise partitioning between two daughter cells during mitosis. Misregulation of the complex mitotic machinery may lead to aneuploidy and genomic instability, known drivers of tumorigenesis. Indeed, systematic genetic analysis of many cancer tissues over the last decades, indicates the presence of severe chromosome abnormalities in thousands of cancer tissue samples. In this work, I investigated the function of two components of ubiquitin signaling, the deubiquitinating enzyme UCHL3 and the E3 ubiquitin ligase TRIM15. The hypothesized role of E3 ligase TRIM15 in the cell cycle regulation could not be confirmed by our experiments, but I observed an effect on cell adhesion and motility instead. UCHL3 was identified using high-content visual siRNA screen, as a critical factor controlling genome segregation and integrity. Interestingly, it has been previously reported that UCHL3 levels are altered in various cancer types, especially colon cancer. My data demonstrate that UCHL3 drives proper alignment of chromosomes at the metaphase plate by facilitating...
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The role of Fam208a during mouse embryogenesis
Bhargava, Shohag ; Chawengsaksophak, Kallayanee (advisor) ; Machoň, Ondřej (referee) ; Macůrková, Marie (referee)
(in English) Post-implantation embryo development proceeds through several key morphogenetic events that are fine-tuned by epigenetic modifications. Gastrulation is one of the most crucial developmental event that occurs during early post-implantation stage resulting in the formation of the three germ layers together with the establishment of the anterior-posterior (A-P) axis. It requires a highly coordinated interaction between the embryonic and extra-embryonic regions of the developing embryo. Gastrulation initiates with the formation of the primitive streak and, during which, cells of the epiblast delaminate and ingress through the primitive streak to form the mesoderm and definitive endoderm. During early post-implantation stages, the pluripotent cell population of the epiblast undergoes very rapid cellular proliferation and extensive epigenetic programming. There are numerous studies emphasizing various signaling molecules, transcription factors and epigenetic machinery maintaining the genomic stability that drive successful gastrulation and any discrepancy or defects almost always results in embryonic lethality. One such newly highlighted silencing machinery is that of the Human silencing hub (HUSH) complex comprising of the core members; FAM208A; H3K9me3-reader, MPP8 and PPHLN that together...
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The roles of Trim15 and UCHL3 in the ubiquitin-mediated cell cycle regulation.
Jeřábková, Kateřina ; Chawengsaksophak, Kallayanee (advisor) ; Šolc, Petr (referee) ; Thorpe, Peter (referee)
(ENGLISH) Ubiquitin signaling is a key regulatory mechanism for many important cellular processes such as transcription, differentiation and cell division. Cell division requires duplication of all genetic material during S-phase followed by its precise partitioning between two daughter cells during mitosis. Misregulation of the complex mitotic machinery may lead to aneuploidy and genomic instability, known drivers of tumorigenesis. Indeed, systematic genetic analysis of many cancer tissues over the last decades, indicates the presence of severe chromosome abnormalities in thousands of cancer tissue samples. In this work, I investigated the function of two components of ubiquitin signaling, the deubiquitinating enzyme UCHL3 and the E3 ubiquitin ligase TRIM15. The hypothesized role of E3 ligase TRIM15 in the cell cycle regulation could not be confirmed by our experiments, but I observed an effect on cell adhesion and motility instead. UCHL3 was identified using high-content visual siRNA screen, as a critical factor controlling genome segregation and integrity. Interestingly, it has been previously reported that UCHL3 levels are altered in various cancer types, especially colon cancer. My data demonstrate that UCHL3 drives proper alignment of chromosomes at the metaphase plate by facilitating...
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The role of Fam208a during mouse embryogenesis
Bhargava, Shohag ; Chawengsaksophak, Kallayanee (advisor) ; Machoň, Ondřej (referee) ; Macůrková, Marie (referee)
(in English) Post-implantation embryo development proceeds through several key morphogenetic events that are fine-tuned by epigenetic modifications. Gastrulation is one of the most crucial developmental event that occurs during early post-implantation stage resulting in the formation of the three germ layers together with the establishment of the anterior-posterior (A-P) axis. It requires a highly coordinated interaction between the embryonic and extra-embryonic regions of the developing embryo. Gastrulation initiates with the formation of the primitive streak and, during which, cells of the epiblast delaminate and ingress through the primitive streak to form the mesoderm and definitive endoderm. During early post-implantation stages, the pluripotent cell population of the epiblast undergoes very rapid cellular proliferation and extensive epigenetic programming. There are numerous studies emphasizing various signaling molecules, transcription factors and epigenetic machinery maintaining the genomic stability that drive successful gastrulation and any discrepancy or defects almost always results in embryonic lethality. One such newly highlighted silencing machinery is that of the Human silencing hub (HUSH) complex comprising of the core members; FAM208A; H3K9me3-reader, MPP8 and PPHLN that together...
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