"Protein modifications in DNA damage signalling: Mechanisms and cancer relevance"@en . . . "DNA damage response; siRNA-based genetic screening; protein ubiquitylation; phosphorylation; oncogen"@en . "0"^^ . . "2008-01-01+01:00"^^ . "0"^^ . "1"^^ . "V souladu s p\u016Fvodn\u00EDmi z\u00E1m\u011Bry na\u0161eho Projektu se n\u00E1m poda\u0159ilo dos\u00E1hnout hlavn\u00EDch c\u00EDl\u016F, jak dokl\u00E1daj\u00ED na\u0161e v\u00FDsledky ve 4 hlavn\u00EDch oblastech (C\u00EDle 1-4) vyt\u010Den\u00FDch v p\u016Fvodn\u00ED aplikaci: 1) Provedli jsme rozs\u00E1hl\u00E9 funk\u010Dn\u011B genetick\u00E9 skr\u00EDningov\u00E9 pokusy a nalezli nov\u00E9 lidsk\u00E9 geny, jejich\u017E produkty jsou v\u00FDznamn\u00E9 pro spr\u00E1vnou odpov\u011B\u010F (nap\u0159. signalizaci nebo opravu) na po\u0161kozen\u00ED DNA; 2) Vybran\u00E9 nov\u00E9 geny byly"@cs . " phosphorylation" . . . . " protein ubiquitylation" . "http://www.isvav.cz/projectDetail.do?rowId=GA301/08/0353"^^ . . . . . . "2010-12-31+01:00"^^ . "Maintenance of genomic integrity is a fundamental biological mechanism that guards against genetic diseases including cancer. Orchestration of DNA damage signaling with cell cycle checkpoints, DNA repair, chromatin modulation and cell death pathways relies on regulatory protein post-translational modifications. Whereas the key role of protein phosphorylation in DNA damage response (DDR) is well established, the significance of ubiquitylation and sumoylation is only emerging. Here, we propose to identify, through targeted siRNA based screens, human genes involved in regulatory ubiquitylation, sumoylation and neddylation within the DDR machinery. Through several screening strategies and functional analysis of the identified gene products, we willelucidate the molecular basis and biological role of such protein modifications in DNA damage signaling and cell fate decisions including cell cycle arrest, DNA repair and cell survival. Factors critical for response to oncogene-evoked replication stress"@en . . . . . "2010-04-01+02:00"^^ . . " siRNA-based genetic screening" . . "7"^^ . "7"^^ . . "Udr\u017Eov\u00E1n\u00ED integrity genomu je z\u00E1kladn\u00EDm biologick\u00FDm mechanismem ochrany proti genetick\u00FDm onemocn\u011Bn\u00EDm v\u010Detn\u011B nador\u016F. Koordinace signalizace po\u0161kozen\u00ED DNA s \u0159\u00EDzen\u00EDm bun\u011B\u010Dn\u00E9ho cyklu, opravou DNA, modulac\u00ED chromatinu a mechanism\u016F bun\u011B\u010Dn\u00E9 smrti je regulov\u00E1na postransla\u010Dn\u00EDmi modifikacemi protein\u016F. Zat\u00EDmco \u00FAloha proteinov\u00FDch fosforylac\u00ED v odpov\u011Bdi na po\u0161kozen\u00ED DNA (d\u00E1le DDR) je dob\u0159e zn\u00E1ma, v\u00FDznam ubikvitinylac\u00ED a sumoylac\u00ED je teprve zji\u0161\u0165ov\u00E1n. N\u00E1vrhem projektu je identifikovat pomoc\u00ED siRNA-c\u00EDlen\u00E9ho skr\u00EDningu lidsk\u00E9 geny \u00FA\u010Dastn\u00EDc\u00ED se regulac\u00ED ubikvitinylace, sumoylace a neddylace b\u011Bhem DDR. Pomoc\u00ED r\u016Fzn\u00FDch prohled\u00E1vac\u00EDch strategi\u00ED a funk\u010Dn\u00ED anal\u00FDzy identifikovan\u00FDch genov\u00FDch produkt\u016F objasn\u00EDme molekul\u00E1rn\u00ED podstatu a biologickou \u00FAlohu tohoto typu proteinov\u00FDch modifikac\u00ED v signalizaci po\u0161kozen\u00ED DNA a v rozhodov\u00E1n\u00ED o osudu bu\u0148ky zahrnuj\u00EDc\u00EDm z\u00E1stavu bun\u011B\u010Dn\u00E9ho cyklu, opravu DNA a jej\u00ED p\u0159e\u017Eit\u00ED. Budeme rovn\u011B\u017E identifikovat faktory \u00FA\u010Dastn\u00EDc\u00ED se reakce na replika\u010Dn\u00ED stres indukovan\u00FD onkogeny a zhodnot\u00EDme mo\u017En\u00E9" . . "DNA damage response" . "2015-02-09+01:00"^^ . "Consistent with the originally identified objectives of this Project, we believe we have achieved the goals, as can be documented by our key results in the 4 major areas of activity, related to Aims 1-4 of the original application: 1) We have performed high-throughput siRNA-based functional genomic screens and identified novel human genes and proteins involved in DNA damage sensing/signaling an"@en . "Modifikace b\u00EDlkovin v signalizaci po\u0161kozen\u00ED DNA: Mechanismy a vztah k n\u00E1dor\u016Fm" . . "GA301/08/0353" .