Regulation of structure-specific endonucleases

Mgr. Alexandra Sisáková, Ph.D.

Doctoral thesis

Abstract:

Homológna rekombinácia je opravný mechanizmus podieľajúci sa na udržovaní stability genómu opravou dvojreťazcových zlomov na DNA. Táto cesta zahŕňa množstvo rôznych faktorov, vrátane štruktúrne-špecifických nukleáz, ktoré sú nevyhnutné pre štiepenie medziproduktov DNA vznikajúcich počas opravy a DNA replikácie. Nukleázy, ako aj ďalšie enzýmy musia byť presne regulované, čo je umožnené v mnohých prípadoch prostredníctvom proteín-proteínových interakcií. Okrem toho, regulácia nukleázovej aktivity našla potenciálne využitie v protinádorovej terapii v kontexte syntetickej letality. V dizertačnej práci sme sa zamerali na endonukleázy yMus81-Mms4 (MUS81-EME1 u ľudí) a MRE11.

Abstract:

Homologous recombination is a repair mechanism involved in the genome integrity maintenance by repairing DNA double strand breaks. This pathway involves a number of different factors, including structure-specific nucleases, which are essential for processing of DNA intermediates arising during the repair and DNA replication. Nucleases, as well as other enzymes must be strictly regulated, which is achieved in many cases through protein-protein interactions. Moreover, the regulation of nuclease activity finds potential use in anticancer therapy in the context of synthetic lethality. In the thesis we are focused on yeast Mus81-Mms4 (MUS81-EME1 in humans) and MRE11 structure-specific endonucleases.

Keywords

homologous recombination, structure-specific endonuclease, MUS81, MRE11, small molecule inhibitors, RFC, common fragile sites, synthetic lethality

Language used: English

Date on which the thesis was submitted / produced: 5. 6. 2017

Thesis defence

• Date of defence: 21. 9. 2017
• Supervisor: doc. Mgr. Lumír Krejčí, Ph.D.

Masaryk University

Faculty of Medicine

Doctoral programme / field:
Medical Biology (4-years) / Medical Biology