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Biofyzikální a funkční charakterisace aspartátových proteas z rodiny proteinů podobných Ddi-1, zapojených do odpovědi na replikační stres / BIOPHYSICAL AND FUNCTIONAL CHARACTERIZATION OF DDI1-LIKE ASPARTIC PROTEASES INVOLVED IN REPLICATION STRESS RESPONSE

Accurate, timely replication of a DNA molecule is a pivotal moment in the life cycle of every living organism. Any temporal or spatial defect putting the fine-tuned replication machinery off balance causes the so-called replication stress. As the replication machinery consists mainly of enzymes and other proteins, it is not surprising that many of the obstacles most severely blocking the replication machinery progress are of protein origin. Therefore, specialized proteases responsible for relieving replication stress matured during evolution. However, neither the full repertoire of proteolytic enzymes and their particular substrates taking place in countering the DNA replication stress nor detailed molecular mechanisms involved remain unknown. This thesis describes how conserved putative aspartic proteases of the Ddi1-like family engage in countering DNA replication stress via a proteolysis dependent mechanism. We structurally and biophysically characterized yeast and human members of the Ddi1-like family, explored their interactions with ubiquitin and polyubiquitin chains, and identified hypersensitivity to DNA replication inhibitor hydroxyurea in a yeast strain double deleted for DDI1 gene together with a DNA dependent metalloprotease WSS1. Detailed analysis of the DDI1 role in hydroxyurea...

Identiferoai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:438371
Date January 2021
CreatorsSvoboda, Michal
ContributorsKonvalinka, Jan, Obšil, Tomáš, Čermák, Lukáš
Source SetsCzech ETDs
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/doctoralThesis
Rightsinfo:eu-repo/semantics/restrictedAccess

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